Breast CancerPhase 1NCT06251544
TRAIL-R2 and HER2 Bi-Specific Chimeric Antigen Receptor (CAR) T Cells for the Treatment of Metastatic Breast Cancer
A Phase 1 study testing HTR2 T Cells in people with Breast Cancer and Tumor, Breast, run by Baylor College of Medicine at 1 site in United States.
Trial summary
The purpose of this study is to find the biggest dose of HTR2 T cells that is safe, to see how long these cells last in the body, to learn the side effects, and to see if these cells are able to fight and kill HER2 expressing breast cancer. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Breast Cancer, Tumor, Breast, Breast Tumor
- What is being tested?
- HTR2 T Cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Aug 2026to Jan 2044
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Procurement Inclusion Criteria:
- Any patient between 18-80 years of age regardless of sex, with a diagnosis of metastatic or locally recurrent unresectable HER2 positive breast cancer.
- HER2 tumor expression1+, 2+ or 3+ by IHC
- The disease must have progressed after standard first line therapy. Patients are still eligible if they have failed more than one line of therapy.
- Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.
Treatment Inclusion Criteria:
- Patients between ages 18 and 80 years old with a diagnosis of either stage IV breast cancer or locally recurrent unresectable breast cancer. Disease must have progressed after standard first line therapy. Patients are still eligible if they have failed more than one line of therapy.
- Measurable or evaluable disease per RECIST 1.1 criteria.
- HER2 tumor expression 1+, 2+ or 3+ by IHC.
- Bilirubin ≤ 3x upper limit of normal.
- AST and ALT ≤ 3x upper limit of normal
- Hemoglobin ≥ 7 g/dl (may be transfused values)
- Serum creatinine < 2 x the upper limit of normal.
- Pulse oximetry of > 90% on room air.
- Off conventional or investigational therapy for 3 weeks prior to study entry.
- ECOG Performance Status ≤ 2
- The patient is able to understand and give informed consent to study related procedures and treatments.
Procurement Exclusion Criteria:
- Known pregnancy or actively breast feeding.
- Active and uncontrolled bacterial, viral, or fungal infection.
- Patients with current use of systemic corticosteroids (Prednisone equivalent >0.5mg/kg/day).
- Patients with abnormal left ventricular function (LVEF <55%)
- Patients with brain metastases that are progressing.
Treatment Exclusion Criteria:
- Pregnant or breast feeding
- Active and uncontrolled bacterial, viral or fungal infection
- Patient with current use of systemic corticosteroids (prednisone equivalent >0.5 mg/kg/day.
- Patients with abnormal left ventricular function (LVEF <55%).
- Patients with brain metastases that are progressing
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
Houston Methodist Hospital
Houston, Texas, 77030
Natalie Chen, MD, 215-534-7895, natalie.chen@bcm.edu
Wendy Callejas, MD, 832-824-1538, wlcalle2@texaschildrens.org
About this study
Official title: (TRAILBLASER) TRAIL-R2 and HER2 Bi-Specific Chimeric Antigen Receptor T Cells for the Treatment of Metastatic Breast Cancer
The purpose of this study is to find the biggest dose of HTR2 T cells that is safe, to see how long these cells last in the body, to learn the side effects, and to see if these cells are able to fight and kill HER2 expressing breast cancer.
Patients eligible for this study have metastatic breast cancer that has HER2 expression and has progressed on at least one line of therapy. This is a gene transfer research study using special immune cells called T cells. T cells are a type of white blood cell that helps the body recognize and fight cancer cells.
Read more
The body has different ways of fighting diseases and no single way seems perfect for fighting cancer. This research combines two different ways of fighting cancer: antibodies and T cells. Antibodies are proteins that protect the body from infectious disease and possibly cancer. T cells, or T lymphocytes, are special blood cells that can kill other cells, including tumor cells. Both antibodies and T cells have shown promise treating cancer but have not been strong enough to cure most patients.
Previous research has found that investigators can put genes into T cells that helps them recognize cancer cells and kill them. Investigators now want to see if by putting a new gene in those T cells to help recognize breast cancer cells expressing HER2 can kill the cancer cells. In clinical trials for various cancer types that express HER2, our center engineered a CAR that recognizes HER2 and put this CAR into patients own T cells and gave them back. Investigators saw that the cells did grow and patients did tolerate and respond to the treatment.
Investigators will add a gene to the HER2 recognizing CAR T cells that will improve the T cells function. Investigators know that some immune cells in the body can lower T cells ability to kill cancer cells. Investigators have identified an antibody that will inactivate those immune suppressive cells thereby allowing T cells to survive better to recognize and kill cancer cells. This antibody targets the Trail-R2 receptor and is referred to as TR2.
Also, investigators know that T cells need the support of cytokines to perform their immune functions. There is evidence showing that the addition of interleukin 15 (IL15) enhances CAR T cells ability to kill cancer cells. As a result, investigators also added IL15 to the HER2 and TR2 targeting CAR T cells (HTR2 T cells).
The HTR2 T cells are an investigational product not approved by the Food and Drug Administration.
Read the detailed description
To make the T cells, the investigators will take the patient's blood and stimulate it with growth factors to make T cells grow. Investigators use a retrovirus to insert HER CAR, TR2 antibody and IL 15 genes into the T cells.
HTR2 cells are generated from the patient's T cells and are frozen. At the time the patient is scheduled to be treated, the cells will then be thawed and injected into the patient over 5 to 10 minutes. Patients will only get one dose of HTR2 T cells during the infusion. If the patient has a good response and tolerance, we may be able to repeat infusion in the future. The patent may be pretreated with Tylenol and Benadryl to prevent possible allergic reaction to the T cell administration.
If investigators need to stop the HTR2 T cells due to bad side effects, investigators have inserted a gene called iCasp9 into the T cells. This allows investigators to eliminate the HTR2 T cells in the blood when the gene comes into contact with a medication called Rimiducid. The drug Rimiducid is not yet FDA approved and is an experimental drug, but it has been tested in humans without bad side-effects. Investigators will only use this drug to kill the T cells if necessary due to side effects. Since investigators do not know exactly what dose will effectively stop HTR2 T cells in individual patients, investigators will start at a low dose with the ability to increase the dose two more times based on how patients are doing. Blood work will be done to ensure that the HTR2 T cells have been successfully eliminated.
The treatment will be given by the Center for Cell and Gene Therapy at Houston Methodist Hospital.
MEDICAL TESTS BEFORE TREATMENT
Before being treated, patients will receive a series of standard medical tests:
- Physical exam and history
- Blood tests to measure blood cells and organ function
- Measurements of the tumor by scans at baseline prior to treatment
- Ultrasound of the heart to make sure the patient has good baseline cardiac function
Additionally, patients will need a biopsy of their tumor tissue to both confirm HER2 expression and to be used for research purposes.
MEDICAL TESTS DURING AND AFTER TREATMENT
Within four weeks after infusion, patients will be monitored on a weekly basis for dose limiting side effects of the HTR2 T cells:
- Physical exam and history
- Blood tests to measure blood cells and organ function
After the initial six weeks, patients will be monitored at a minimum every 3 months for the 1st year and every 6 months between 1 to year 5 or as frequently as deemed necessary:
- Physical exam and history
- Blood tests to measure blood cells and organ function
- Measurements of patient's tumor by scans to assess treatment response
To learn more about the way T cells work in the patient's body, investigators will obtain up to 50 ml of blood from patient before chemotherapy, before the T-cell infusion, 1 to 4 hours, 1, 2, 3, 4 weeks and 8 weeks after infusion, every 3 months for a year followed by every 6 months for 4 years and then every year for the the next 10 years. Total participation on this study will be 15 years. During the time points listed above, if the T cells are found in the blood at a certain amount, an extra half a tablespoon of blood may be needed for additional testing.
Investigators will obtain one tissue biopsy within 4 weeks after infusion and as clinically indicated thereafter. If additional clinically indicated tumor biopsies are obtained, investigators will ask for a portion of the sample for research.
- Conditions
- Breast Cancer, Tumor, Breast, Breast Tumor, Malignant Neoplasm of Breast, Mammary Cancer, Mammary Neoplasm
- Being tested
- HTR2 T Cells
- Keywords
- HER2 positive
- Medical subject headings
- Breast Neoplasms, Mammary Neoplasms, Animal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HTR2 T CellsGenetic
Arm A -- Two dose levels will be evaluated:
Dose level One: 1.00E+06
Dose level Two: 1.00E+07
HTR2 T CellsGenetic
Arm B -- Two dose levels will be evaluated:
Dose level Two: 1.00E+07
Dose Level Three: 1.00E+08
| Study group | Role | What they receive |
|---|---|---|
| Arm A: HTR2 T Cells (without lymphodepletion) | Experimental | Two dose levels will be evaluated in Arm A (without lymphodepletion) Receives: Genetic: HTR2 T Cells |
| Arm B: HTR2 T Cells (with lymphodepletion) | Experimental | Two dose levels will be evaluated in Arm B (with lymphodepletion) Receives: Genetic: HTR2 T Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting toxicity (DLT) rate
Rate of incidents of dose limiting toxicity by dose levels.
Measured: 4 weeks after first infusion
Secondary outcomes (1)
Objective response rate (ORR)
Proportion of subjects with best overall response of complete response (CR) or partial response (PR) according to RECIST criteria
Measured: 3 months after first infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2024
- Study start3 Aug 2026
- Primary completionJan 2029 (estimated)
- Study completionJan 2044 (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 Baylor College of MedicineThe 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 27 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital Research Institute
- Responsible party
- Principal investigator, Natalie Chen, Baylor College of Medicine
- Investigators
- Natalie Chen, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06251544
- Sponsor's protocol ID
- H-54673 TRAILBLASER
- Status last verified
- Sep 2026
- First submitted
- 1 Feb 2024
- Last updated
- 24 Sep 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 24 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- (TRAILBLASER) TRAIL-R2 and HER2 Bi-Specific Chimeric Antigen Receptor T Cells for the Treatment of Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT06251544
- Acronym / sponsor ID
- H-54673 TRAILBLASER
- Conditions
- Breast Cancer, Tumor, Breast, Breast Tumor, Malignant Neoplasm of Breast, Mammary Cancer, Mammary Neoplasm
- Keywords
- HER2 positive
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 27 participants (estimated)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Collaborators
- Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital Research Institute
- Study start
- 3 Aug 2026 (actual)
- Primary completion
- Jan 2029 (estimated)
- Study completion
- Jan 2044 (estimated)
- First posted
- 9 Feb 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.
The purpose of this study is to find the biggest dose of HTR2 T cells that is safe, to see how long these cells last in the body, to learn the side effects, and to see if these cells are able to fight and kill HER2 expressing breast cancer.
Patients eligible for this study have metastatic breast cancer that has HER2 expression and has progressed on at least one line of therapy. This is a gene transfer research study using special immune cells called T cells. T cells are a type of white blood cell that helps the body recognize and fight cancer cells.
The body has different ways of fighting diseases and no single way seems perfect for fighting cancer. This research combines two different ways of fighting cancer: antibodies and T cells. Antibodies are proteins that protect the body from infectious disease and possibly cancer. T cells, or T lymphocytes, are special blood cells that can kill other cells, including tumor cells. Both antibodies and T cells have shown promise treating cancer but have not been strong enough to cure most patients.
Previous research has found that investigators can put genes into T cells that helps them recognize cancer cells and kill them. Investigators now want to see if by putting a new gene in those T cells to help recognize breast cancer cells expressing HER2 can kill the cancer cells. In clinical trials for various cancer types that express HER2, our center engineered a CAR that recognizes HER2 and put this CAR into patients own T cells and gave them back. Investigators saw that the cells did grow and patients did tolerate and respond to the treatment.
Investigators will add a gene to the HER2 recognizing CAR T cells that will improve the T cells function. Investigators know that some immune cells in the body can lower T cells ability to kill cancer cells. Investigators have identified an antibody that will inactivate those immune suppressive cells thereby allowing T cells to survive better to recognize and kill cancer cells. This antibody targets the Trail-R2 receptor and is referred to as TR2.
Also, investigators know that T cells need the support of cytokines to perform their immune functions. There is evidence showing that the addition of interleukin 15 (IL15) enhances CAR T cells ability to kill cancer cells. As a result, investigators also added IL15 to the HER2 and TR2 targeting CAR T cells (HTR2 T cells).
The HTR2 T cells are an investigational product not approved by the Food and Drug Administration.
Detailed description
To make the T cells, the investigators will take the patient's blood and stimulate it with growth factors to make T cells grow. Investigators use a retrovirus to insert HER CAR, TR2 antibody and IL 15 genes into the T cells.
HTR2 cells are generated from the patient's T cells and are frozen. At the time the patient is scheduled to be treated, the cells will then be thawed and injected into the patient over 5 to 10 minutes. Patients will only get one dose of HTR2 T cells during the infusion. If the patient has a good response and tolerance, we may be able to repeat infusion in the future. The patent may be pretreated with Tylenol and Benadryl to prevent possible allergic reaction to the T cell administration.
If investigators need to stop the HTR2 T cells due to bad side effects, investigators have inserted a gene called iCasp9 into the T cells. This allows investigators to eliminate the HTR2 T cells in the blood when the gene comes into contact with a medication called Rimiducid. The drug Rimiducid is not yet FDA approved and is an experimental drug, but it has been tested in humans without bad side-effects. Investigators will only use this drug to kill the T cells if necessary due to side effects. Since investigators do not know exactly what dose will effectively stop HTR2 T cells in individual patients, investigators will start at a low dose with the ability to increase the dose two more times based on how patients are doing. Blood work will be done to ensure that the HTR2 T cells have been successfully eliminated.
The treatment will be given by the Center for Cell and Gene Therapy at Houston Methodist Hospital.
MEDICAL TESTS BEFORE TREATMENT
Before being treated, patients will receive a series of standard medical tests:
- Physical exam and history
- Blood tests to measure blood cells and organ function
- Measurements of the tumor by scans at baseline prior to treatment
- Ultrasound of the heart to make sure the patient has good baseline cardiac function
Additionally, patients will need a biopsy of their tumor tissue to both confirm HER2 expression and to be used for research purposes.
MEDICAL TESTS DURING AND AFTER TREATMENT
Within four weeks after infusion, patients will be monitored on a weekly basis for dose limiting side effects of the HTR2 T cells:
- Physical exam and history
- Blood tests to measure blood cells and organ function
After the initial six weeks, patients will be monitored at a minimum every 3 months for the 1st year and every 6 months between 1 to year 5 or as frequently as deemed necessary:
- Physical exam and history
- Blood tests to measure blood cells and organ function
- Measurements of patient's tumor by scans to assess treatment response
To learn more about the way T cells work in the patient's body, investigators will obtain up to 50 ml of blood from patient before chemotherapy, before the T-cell infusion, 1 to 4 hours, 1, 2, 3, 4 weeks and 8 weeks after infusion, every 3 months for a year followed by every 6 months for 4 years and then every year for the the next 10 years. Total participation on this study will be 15 years. During the time points listed above, if the T cells are found in the blood at a certain amount, an extra half a tablespoon of blood may be needed for additional testing.
Investigators will obtain one tissue biopsy within 4 weeks after infusion and as clinically indicated thereafter. If additional clinically indicated tumor biopsies are obtained, investigators will ask for a portion of the sample for research.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: HTR2 T Cells (without lymphodepletion) | Experimental | Genetic: HTR2 T CellsTwo dose levels will be evaluated in Arm A (without lymphodepletion) |
| Arm B: HTR2 T Cells (with lymphodepletion) | Experimental | Genetic: HTR2 T CellsTwo dose levels will be evaluated in Arm B (with lymphodepletion) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| HTR2 T CellsArm A -- Two dose levels will be evaluated: Dose level One: 1.00E+06 Dose level Two: 1.00E+07 | Genetic | Arm A: HTR2 T Cells (without lymphodepletion) |
| HTR2 T CellsArm B -- Two dose levels will be evaluated: Dose level Two: 1.00E+07 Dose Level Three: 1.00E+08 | Genetic | Arm B: HTR2 T Cells (with lymphodepletion) |
Primary outcome
Dose-limiting toxicity (DLT) rate
Time frame: 4 weeks after first infusion
Rate of incidents of dose limiting toxicity by dose levels.
1 secondary outcome
Objective response rate (ORR)
Time frame: 3 months after first infusion
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 24 Sep 2026.
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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.
Natalie Chen, MD principal investigator
Baylor College of Medicine
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 HTR2 T Cells in people with Breast Cancer and Tumor, Breast, run by Baylor College of Medicine 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?
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 24 Sep 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 Natalie Chen, MD (215-534-7895, natalie.chen@bcm.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-limiting toxicity (DLT) rate (time frame: 4 weeks after first infusion). 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 24 Sep 2026; AzTrials last refreshed its copy on 6 Nov 2026.