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

NCT06347068 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: LCCC2128-ATLP50CA058223-29A1
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Breast Cancer; Relapse; Resistant Cancer; Triple Negative Breast Cancer

Keywords

cellular therapy; biologic therapy

Outcome Measures

Primary Outcomes (3)

• Toxicity: NCI-CTCAE

  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)

  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

• Toxicity: Immune effector cell-associated neurotoxicity syndrome (ICANS)

  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

Secondary Outcomes (7)

• The recommended phase 2 dose (RP2D) NCI-CTCAE v5.

  Up to 4 weeks

• The recommended phase 2 dose (RP2D) CRS Grading

  Up to 4 weeks

• The recommended phase 2 dose (RP2D)

  Up to 4 weeks

• Objective response rate

  Up to 2 years

• Progression Free Survival (PFS)

  Up to 2 years

Study Arms (1)

iC9-CAR.B7-H3 T cells

EXPERIMENTAL

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; Drug: cyclophosphamide; Drug: fludarabine

Interventions

iC9-CAR.B7-H3 T Cell Therapy BIOLOGICAL

iC9-CAR.B7-H3 T cells will then be administered intravenously

Also known as: iC9-CAR.B7-H3 T cells

iC9-CAR.B7-H3 T cells

cyclophosphamide DRUG

cyclophosphamide 300 mg/m2 IV will be given.

Also known as: Cytoxan

iC9-CAR.B7-H3 T cells

fludarabine DRUG

fludarabine 30 mg/m2 IV will be given.

Also known as: Fludara, Fludarabine Phosphate

iC9-CAR.B7-H3 T cells

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Unless otherwise noted, subjects must meet all of the following criteria to participate in in all phases of the study:
• 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.
• Age ≥ 18 years at the time of consent.
• Karnofsky score of \> 60% (see APPENDIX VI- Karnofsky Scale))
• Histologically confirmed TNBC (ER-, PR-, HER2-negative)
• ER- and PR-negative: defined as \< 1% staining by immunohistochemistry (IHC)
• HER2-negative: defined as IHC 0-1+ or fluorescence in situ hybridization (FISH) ratio \< 2.0

You may not qualify if:

• Patients with a history of symptomatic CNS involvement or multiple metastases requiring whole-brain radiation.
• 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.
• Subject does not have a measurable and or evaluable disease as defined by RECIST 1.1

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• M.D. Anderson Cancer Center: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Related Links

• University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials

MeSH Terms

Conditions

Breast Neoplasms; Recurrence; Triple Negative Breast Neoplasms

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Yara E Abdou, MD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Caroline Babinec

CONTACT

919-445-4208; UNCImmunotherapy@med.unc.edu

Catherine Cheng

CONTACT

+1 919-445-4208; UNCImmunotherapy@med.unc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2024
• First Posted: April 4, 2024
• Study Start: June 27, 2024
• Primary Completion: May 1, 2026
• Study Completion (Estimated): May 1, 2028
• Last Updated: April 22, 2026

Record last verified: 2026-04

Locations

US (1)