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

Summary

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.

Conditions

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

Interventions

GENETIC

T cells or CAR T cells

There are 2 dose levels: Dose Level 1 (1x10\^8 cells/m2) and Dose Level -1 (5x10\^7 cells/m2). In the event that Dose Level 1 is not tolerable, de-escalation to Dose Level -1 will occur.

DRUG

Pembrolizumab Injectable Product

2 mg/kg/dose (max 200 mg/dose) every 3 weeks

DRUG

Nivolumab Injectable Product

3 mg/kg/dose (\<40kg) or 124 mg (≥40 kg) every 2 weeks

Sponsors & Collaborators

• Center for Cell and Gene Therapy, Baylor College of Medicine

  collaborator OTHER

• The Faris Foundation USA

  collaborator UNKNOWN

• Stand Up To Cancer

  collaborator OTHER

• Triumph Over Kid Cancer Foundation

  collaborator UNKNOWN

• St. Baldrick's Foundation

  collaborator OTHER

• National Cancer Institute (NCI)

  collaborator NIH

• Baylor College of Medicine

  lead OTHER

Principal Investigators

• Meenakshi Hegde, MD · Baylor College of Medicine

• Shoba Navai, MD · Baylor College of Medicine

• Nabil Ahmed, MD · Baylor College of Medicine

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

1 Year

Max Age

25 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-12-07

Primary Completion

2028-06-30

Completion

2043-06-30

FDA Drug

Yes

Countries

• United States

Study Locations