Breast CancerPhase 1NCT06347068
Study of Autologous CAR-T Cells Targeting B7-H3 in TNBC iC9-CAR.B7-H3 T Cells
A Phase 1 study testing iC9-CAR.B7-H3 T Cell Therapy, cyclophosphamide and fludarabine in people with Breast Cancer and Relapse, run by UNC Lineberger Comprehensive Cancer Center at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Relapse, Resistant Cancer
- What is being tested?
- iC9-CAR.B7-H3 T Cell Therapy, cyclophosphamide and fludarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Jun 2024to May 2030
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of North Carolina
Chapel Hill, North Carolina, 27599
Catherine Cheng, 919-445-4208, catherine_cheng@med.unc.edu
Yara Abdou, MD
About this study
Official title: 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).
Read the 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.
- Being tested
- iC9-CAR.B7-H3 T Cell Therapy, cyclophosphamide, fludarabine
- Keywords
- cellular therapy, biologic therapy
- Medical subject headings
- Breast Neoplasms, Recurrence, Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
iC9-CAR.B7-H3 T Cell TherapyBiological
Also called iC9-CAR.B7-H3 T cells
iC9-CAR.B7-H3 T cells will then be administered intravenously
cyclophosphamideDrug
Also called Cytoxan
cyclophosphamide 300 mg/m2 IV will be given.
fludarabineDrug
Also called Fludara, Fludarabine Phosphate
fludarabine 30 mg/m2 IV will be given.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: iC9-CAR.B7-H3 T Cell Therapy; Drug: cyclophosphamide; Drug: fludarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 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).
Measured: Up to 4 weeks
Secondary outcomes (7)
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.
Measured: Up to 4 weeks
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.
Measured: Up to 4 weeks
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.
Measured: Up to 4 weeks
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.
Measured: Up to 2 years
Progression Free Survival (PFS)
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.
Measured: Up to 2 years
Overall Survival (OS)
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.
Measured: Up to 2 years
Duration of Response (DOR)
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.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2024
- Study start27 Jun 2024
- Primary completion22 May 2028 (estimated)
- Study completionMay 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by UNC Lineberger Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- UNC Lineberger Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), M.D. Anderson Cancer Center
- Responsible party
- Sponsor
- Investigators
- Yara Abdou, MD, Principal investigator, UNC Lineberger Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06347068
- Sponsor's protocol ID
- LCCC2128-ATL
- Other IDs
- P50CA058223-29A1
- Status last verified
- Jul 2026
- First submitted
- 22 Mar 2024
- Last updated
- 28 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06347068
- Acronym / sponsor ID
- LCCC2128-ATL
- Keywords
- cellular therapy, biologic therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- UNC Lineberger Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), M.D. Anderson Cancer Center
- Study start
- 27 Jun 2024 (actual)
- Primary completion
- 22 May 2028 (estimated)
- Study completion
- May 2030 (estimated)
- First posted
- 4 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| iC9-CAR.B7-H3 T cells | Experimental | Biological: iC9-CAR.B7-H3 T Cell Therapy, Drug: cyclophosphamide, Drug: fludarabineSpecimen 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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)
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| iC9-CAR.B7-H3 T Cell TherapyAlso: iC9-CAR.B7-H3 T cellsiC9-CAR.B7-H3 T cells will then be administered intravenously | Biological | iC9-CAR.B7-H3 T cells |
| cyclophosphamideAlso: Cytoxancyclophosphamide 300 mg/m2 IV will be given. | Drug | iC9-CAR.B7-H3 T cells |
| fludarabineAlso: Fludara, Fludarabine Phosphatefludarabine 30 mg/m2 IV will be given. | Drug | iC9-CAR.B7-H3 T cells |
Primary outcome
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.
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
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).
7 secondary outcomes
The recommended phase 2 dose (RP2D) NCI-CTCAE v5.
Time frame: Up to 4 weeks
The recommended phase 2 dose (RP2D) CRS Grading
Time frame: Up to 4 weeks
The recommended phase 2 dose (RP2D)
Time frame: Up to 4 weeks
Objective response rate
Time frame: Up to 2 years
Progression Free Survival (PFS)
Time frame: Up to 2 years
Overall Survival (OS)
Time frame: Up to 2 years
Duration of Response (DOR)
Time frame: Up to 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2026.
- University of North Carolina Lineberger Comprehensive Cancer Center Clinical TrialsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Yara Abdou, MD principal investigator
UNC Lineberger Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing iC9-CAR.B7-H3 T Cell Therapy, cyclophosphamide and fludarabine in people with Breast Cancer and Relapse, run by UNC Lineberger Comprehensive Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 28 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Caroline Babinec (919-445-4208, UNCImmunotherapy@med.unc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Toxicity: NCI-CTCAE (time frame: Up to 4 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2026.