TRAIL-R2 and HER2 Bi-Specific Chimeric Antigen Receptor (CAR) T Cells for the Treatment of Metastatic Breast Cancer

NCT06251544 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: H-54673 TRAILBLASER
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Tumor, Breast; Breast Tumor; Malignant Neoplasm of Breast; Mammary Cancer; Mammary Neoplasm; Mammary Neoplasms, Human; Neoplasm, Breast; Breast Cancer

Keywords

HER2 positive

Outcome Measures

Primary Outcomes (1)

• Dose-limiting toxicity (DLT) rate

  Rate of incidents of dose limiting toxicity by dose levels.

  4 weeks after first infusion

Secondary Outcomes (1)

• Objective response rate (ORR)

  3 months after first infusion

Study Arms (2)

Arm A: HTR2 T Cells (without lymphodepletion)

EXPERIMENTAL

Two dose levels will be evaluated in Arm A (without lymphodepletion)

Genetic: HTR2 T Cells

Arm B: HTR2 T Cells (with lymphodepletion)

EXPERIMENTAL

Two dose levels will be evaluated in Arm B (with lymphodepletion)

Genetic: HTR2 T Cells

Interventions

HTR2 T Cells GENETIC

Arm A -- Two dose levels will be evaluated: Dose level One: 1.00E+06 Dose level Two: 1.00E+07

Arm A: HTR2 T Cells (without lymphodepletion)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator
• The Methodist Hospital Research Institute: collaborator

Study Sites (1)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Mammary Neoplasms, Animal

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Animal Diseases

Study Officials

• Natalie Chen, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Natalie Chen, MD

CONTACT

215-534-7895; natalie.chen@bcm.edu

Wendy Callejas

CONTACT

832-824-1538; wlcalle2@texaschildrens.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: February 1, 2024
• First Posted: February 9, 2024
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2044
• Last Updated: March 4, 2026

Record last verified: 2026-02

Locations

US (1)