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

ConditionsBreast CancerRelapseResistant CancerTriple Negative Breast Cancer
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorUNC Lineberger Comprehensive Cancer Center

About this trial

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).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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)

Disqualifiers

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

Trial design

Design model

Single group

Treatments tested in this trial

  • iC9-CAR.B7-H3 T Cell Therapy

    Biological/Vaccine

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

  • cyclophosphamide

    Drug

    cyclophosphamide 300 mg/m2 IV will be given.

  • fludarabine

    Drug

    fludarabine 30 mg/m2 IV will be given.

Treatment groups

42 Participants
are divided into 1 treatment group
Group A: iC9-CAR.B7-H3 T cellsExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

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.

Time frame
Up to 4 weeks
2

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

Time frame
Up to 8 weeks after infusion of Biological/Vaccine
3

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).

Time frame
Up to 4 weeks

Secondary outcomes

1

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

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.

Time frame
Up to 4 weeks
2

The recommended phase 2 dose (RP2D) CRS Grading

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.

Time frame
Up to 4 weeks
3

The recommended phase 2 dose (RP2D)

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.

Time frame
Up to 4 weeks
4

Objective response rate

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.

Time frame
Up to 2 years

Other outcomes

Sponsors and contacts

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

UNC Lineberger Comprehensive Cancer Center

Lead sponsor

National Cancer Institute (NCI)

Collaborator

M.D. Anderson Cancer Center

Collaborator

Source ClinicalTrials.gov
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