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HER2 CAR T-cell Therapy with Immunotherapy for Sarcoma

This study is testing a new treatment for advanced sarcoma that has too much HER2 protein. It combines special immune cells called HER2 CAR T cells with either pembrolizumab or nivolumab, which are drugs that help your immune system fight cancer. Researchers want to see if this combination is safe, what side effects it causes, and if it can help patients with sarcomas like osteosarcoma, rhabdomyosarcoma, and Ewing sarcoma. They also want to understand how gut bacteria might affect treatment success. You may be eligible if you are between 1 and 25 years old and have HER2-positive sarcoma. The study plans to enroll 25 participants.

Study design
This is an interventional study with an unclear phase, aiming to enroll 25 participants. It involves two different treatment arms, each testing a combination of HER2 CAR T cells with a different immunotherapy drug.
What's involved
You will first provide blood to create the HER2 CAR T cells. Before receiving these cells, you will get chemotherapy (cyclophosphamide and fludarabine). The HER2 CAR T cells will be given intravenously, and you will be monitored for up to 4 hours afterward.
Compensation
Not stated in the trial record.
Follow-up
You will be followed for a total of 15 years after receiving the gene-modified cells to monitor for long-term side effects.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

NCT04995003

HER2 Chimeric Antigen Receptor (CAR) T Cells in Combination With Checkpoint Blockade in Patients With Advanced Sarcoma

Recruiting
PHASE1Ages 1–25InterventionalTreatment
Baylor College of Medicine
~25 participants
Updated 2026-01-22 on ClinicalTrials.gov
What's tested:T cells or CAR T cellsPembrolizumab Injectable ProductNivolumab Injectable Product

At a glance

Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
ARM A: Dose-limiting toxicity (DLT) rate by CTCAE v5.0. Neurotoxicity and cytokine release syndrome (CRS) will be graded according to ASTCT Consensus Grading System.
Measured over By day 42 or 14 days after second dose of Pembrolizumab (whichever is longer)
+1 more outcome measured

Conditions

Sarcoma
HER-2 Protein Overexpression
Osteosarcoma
Rhabdomyosarcoma
Ewing Sarcoma
Synovial Sarcoma
Soft Tissue Sarcoma
Undifferentiated Sarcoma

Explore related trials

Ewing SarcomaOsteosarcomaRhabdomyosarcomaSarcomaSoft Tissue SarcomaSynovial SarcomaUndifferentiated Soft Tissue SarcomaERBB2 Gene

Where it's being run

1 sites across 1 states
Texas1

Study leadership

  • Meenakshi Hegde, MD · PRINCIPAL_INVESTIGATOR · Baylor College of Medicine
  • Shoba Navai, MD · PRINCIPAL_INVESTIGATOR · Baylor College of Medicine
  • Nabil Ahmed, MD · PRINCIPAL_INVESTIGATOR · Baylor College of Medicine

Who to contact

Meenakshi Hegde, MD
[email protected]
832-824-4840
Email the study team

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Do you actually qualify for this trial?

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Eligibility criteria

Inclusion

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.
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.

Exclusion

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.
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
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

What this trial measures

  • ARM A: Dose-limiting toxicity (DLT) rate by CTCAE v5.0. Neurotoxicity and cytokine release syndrome (CRS) will be graded according to ASTCT Consensus Grading System.By day 42 or 14 days after second dose of Pembrolizumab (whichever is longer)

    Any grade 5 event, Grade 3 and 4 cytokine release syndrome (CRS) or neurological toxicities that fail to return to grade 2 within 5 days of T cell infusion , and all other grade 3 or 4 toxicities (including allergic reactions to T cell infusions) that fail to return to grade 2 within 72 hours. In the event that the combination treatment potentiates expected, severe toxicities attributable to PD-1 antibody, investigators will employ an additional stopping rule which will be applied to each arm separately. If (1) two within the initial six patients treated or (2) greater than 33% of all patients thereafter develop greater than or equal to grade 3 non-hematologic, non-dermatologic toxicity attributable to PD-1 antibody but not attributable to HER2 CAR T cells during the DLT window, investigators will pause enrollment to that study arm. Toxicity will be evaluated according to the CTCAE v5.0 except for CRS and neurotoxicity.

  • ARM B: Dose-limiting toxicity (DLT) rate by CTCAE v5.0. Neurotoxicity and cytokine release syndrome (CRS) will be graded according to ASTCT Consensus Grading System.By day 42 or 7 days after third dose of Nivolumab (whichever is longer)

    Any grade 5 event, Grade 3 and 4 cytokine release syndrome (CRS) or neurological toxicities that fail to return to grade 2 within 5 days of T cell infusion , and all other grade 3 or 4 toxicities (including allergic reactions to T cell infusions) that fail to return to grade 2 within 72 hours. In the event that the combination treatment potentiates expected, severe toxicities attributable to PD-1 antibody, investigators will employ an additional stopping rule which will be applied to each arm separately. If (1) two within the initial six patients treated or (2) greater than 33% of all patients thereafter develop greater than or equal to grade 3 non-hematologic, non-dermatologic toxicity attributable to PD-1 antibody but not attributable to HER2 CAR T cells during the DLT window, investigators will pause enrollment to that study arm. Toxicity will be evaluated according to the CTCAE v5.0 except for CRS and neurotoxicity.