NCT04995003 · Baylor College of Medicine
HER2 Chimeric Antigen Receptor (CAR) T Cells in Combination With Checkpoint Blockade in Patients With Advanced Sarcoma
What this study is about
The purpose of this study is to learn whether it is safe to give HER2-CAR T cells in combination with an immune checkpoint inhibitor drug (pembrolizumab or nivolumab), to learn what the side effects are, and to see whether this therapy might help patients with sarcoma.
View original scientific description
The purpose of this study is to learn whether it is safe to give HER2-CAR T cells in combination with an immune checkpoint inhibitor drug (pembrolizumab or nivolumab), to learn what the side effects are, and to see whether this therapy might help patients with sarcoma. Another goal of this study is to study the bacteria found in the stool of patients with sarcoma who are being treated with HER2 CAR T cells and immune checkpoint inhibitor drugs to see if the types of bacteria influence how well the treatment works. The investigators have found from previous research that they can put a new gene into T cells that will make them recognize cancer cells and kill them. They now want to see if they can put a new gene in these cells that will let the T cells recognize and kill sarcoma cells. The new gene that the investigators will put in makes an antibody specific for HER2 (Human Epidermal Growth Factor Receptor 2) that binds to sarcoma cells. In addition, it contains CD28, which stimulated T cells and make them last longer. After this new gene is put into the T cell, the T cell becomes known as a chimeric antigen receptor T cell or CAR T cell. In another clinical study using these CAR T cells targeting HER2 as well as other studies using CAR T cells, investigators found that giving chemotherapy before the T cell infusion can improve the effect the T cells can have. Giving chemotherapy before a T cell infusion is called lymphodepletion since the chemotherapy is specifically chosen to decrease the number of lymphocytes in the body. Decreasing the number of the patient's lymphocytes first should allow the infused T cells to expand in the body, and potentially kill cancer cells more effectively. The chemotherapy used for lymphodepletion is a combination of cyclophosphamide and fludarabine. After the patient receives the lymphodepletion chemotherapy and CAR T cells during treatment on the study, they will receive an antibody drug called an immune checkpoint inhibitor, pembrolizumab or nivolumab. Immune checkpoint inhibitors are drugs that remove the brakes on the immune system to allow it to act against cancer.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Diagnosis of a HER2-positive sarcoma. Immunohistochemistry (IHC) will be used to determine HER2 expression. Standard HER2 positive breast cancer density gradient tissue microarrays will be used as positive controls. HER2 expression will be graded for percent positive tumor cells (Grade 0: no staining; Grade 1: 1-25%; Grade 2: 26-50% and Grade 3: 51-100%) and intensity of staining (Negative; 1+; 2+; and 3+). For the patient to meet eligibility, tumors are required to have at least ≥ grade 1 and ≥ 1+ intensity score for HER2 staining.
- Age between 1 to 25 years
- Karnofsky or Lansky performance score of ≥ 60
- Informed consent explained to, understood by, and signed by patient/guardian. Patient or guardian given copy of informed consent. Treatment Inclusion Criteria:
- Diagnosis of a HER2 positive sarcoma with active disease progression or recurrence after at least one prior systemic therapy
- At least 4 weeks from and having recovered from acute toxic effects of all prior cytotoxic chemotherapy. Those receiving targeted (non-cytotoxic) drugs must be at least 7 days or 3 drug half-lives, whichever is greater, from last receipt of said drug and must have recovered from all acute toxic effects of that drug.
- Normal cardiac left ventricular end diastolic function (LVEF) as measured by echocardiogram (normal per institutional limits)
- Karnofsky or Lansky performance score of ≥60
- Total bilirubin ≤1.5x upper limit of normal (ULN) for age AND direct bilirubin ≤ULN for age
- AST/ALT ≤ 2.5x ULN
- Serum creatinine ≤1.5x ULN for age
- Hgb ≥ 7.0 g/dL (transfusion allowed)
- WBC \> 2,000/µl
- ANC \>1,000/ul
- Platelets \>75,000/ul (not transfused)
- Pulse oximetry of ≥ 90% on room air
- Sexually active males and females of childbearing potential must agree to use a form of contraception considered effective and medically acceptable by the investigator. Non-childbearing potential is defined as pre-menarche, greater than 1-year post-menopausal, or surgically sterilized.
- Available autologous transduced cytotoxic T lymphocytes with ≥ 15% expression of HER2 CAR and killing of HER2-positive targets ≥ 20% in cytotoxicity assay
- Informed consent explained to, understood by, and signed by patient or guardian. Patient or guardian given copy of informed consent. Procurement
Exclusion criteria
- Known HIV positivity
- Severe previous toxicity from cyclophosphamide including, but not limited to, decreased heart function, abnormal heart rhythms, severe allergic reaction, or grade 4 hemorrhagic cystitis
- Severe previous toxicity from fludarabine including, but not limited to, neurotoxicity, coma, renal injury requiring dialysis, development of hemolytic anemia, or development of a secondary malignancy
- Severe hypersensitivity (≥Grade 3) to pembrolizumab or nivolumab or any of their excipients
- History of allergic reactions attributed to murine protein containing products, DMSO or dextran 40
- Known, active cardiac disorder defined as left ventricular ejection fraction below the institution normal as determined by echocardiogram or New York Heart Association (NYHA) functional class III or IV or clinically significant cardiac arrhythmia. Note: A new echocardiogram or EKG is not required to make this determination.
- Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
- History of non-infectious pneumonitis that required steroids or current pneumonitis
- Known history of active tuberculosis
- Has undergone solid organ transplantation at any time
- Has a diagnosis of immunodeficiency or is receiving any other form of immunosuppressive therapy aside from cytotoxic chemotherapy
- Presence of bulky tumor at the primary or metastatic site
- Has a history or current evidence of any condition, therapy, or laboratory or radiologic abnormality that is not in the best interest of the subject to participate, as determined by the treating investigator Treatment Exclusion Criteria:
- Known HIV positivity
- Intercurrent infection
- Pregnant or lactating
- History of hypersensitivity to murine protein-containing products, DMSO or dextran 40
- Severe previous toxicity from cyclophosphamide including, but not limited to, decreased heart function, abnormal heart rhythms, severe allergic reaction, or grade 4 hemorrhagic cystitis
- Severe previous toxicity from fludarabine including, but not limited to, neurotoxicity, coma, renal injury requiring dialysis, development of hemolytic anemia, or development of a secondary malignancy
- Severe hypersensitivity (≥Grade 3) to pembrolizumab or nivolumab or any of their excipients
- Cardiac disorder defined as left ventricular ejection fraction below the institution normal as determined by echocardiogram or New York Heart Association (NYHA) functional class III or IV or clinically significant cardiac arrhythmia
- Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- History of non-infectious pneumonitis that required steroids or current pneumonitis
- Known history of active tuberculosis
- Has received a live virus vaccine within previous 30 days
- Has undergone solid organ transplantation at any time
- Has a diagnosis of immunodeficiency or is receiving any other form of immunosuppressive therapy
- Presence of bulky tumor at the primary or metastatic site
- Has received radiotherapy within 14 days of start of trial treatment with the exception that those who have received palliative radiation (≤ 10 days of radiotherapy) to non-central nervous system disease within 7 days are permitted. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
- Has a history or current evidence of any condition, therapy, or laboratory or radiologic abnormality that is not in the best interest of the subject to participate, as determined by the treating investigator
Where
- Houston, Texas
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jan 22, 2026 · Source of record for eligibility and locations