3CAR: B7-H3-specific CAR T-cell Therapy for Children and Young Adults with Solid Tumors

Brief Summary

3CAR is a phase 1 clinical trial evaluating the safety and efficacy of autologous B7-H3-specific CAR T-cell therapy for children and young adults with relapsed or refractory solid tumors.

Immunotherapy for solid tumors may help improve patient outcomes because immune therapies are tumor-specific and exhibit non-overlapping cytotoxic mechanisms compared to conventional chemotherapeutic agents.

B7-H3, also called CD276, is a tumor-associated antigen that is an attractive immunotherapy target due to its high expression on multiple different pediatric solid tumors. Evidence suggests it has limited or no expression on most normal tissues. Preclinical data generated by our group and others has shown promising results for B7-H3-CAR T-cell treatment of solid tumors.

Primary Objectives

Primary objective

• To determine the safety and maximum tolerated dose of one intravenous infusion of autologous, B7-H3-CAR T cells in patients 21 years old and younger with relapsed or refractory B7-H3-positive solid tumors after lymphodepleting chemotherapy

Secondary objective

• To evaluate the antitumor activity of B7-H3-CAR T cells

Eligibility

Inclusion criteria

• 21 years old or younger*
• Relapsed or refractory B7-H3-positive solid tumor
• Measurable disease
• Adequate heart, lung, liver, kidney and bone marrow function

*First 3 patients must be at least 12 years old.

Exclusion criteria

• History of HIV infection
• Therapy that will interfere with B7-H3-CAR T-cell function within 14 days prior to CAR T cell infusion
• Rapidly progressing disease
• Known underlying medical condition for which participation would not be in the best interest of the participant or that could prevent, limit or confound protocol assessments

Study Sites

St. Jude Children’s Research Hospital, Memphis, Tennessee

About this study

This study looks at a new treatment for children and young adults with solid tumors that have been difficult to treat (refractory) or have come back after treatment (relapsed).

The new treatment is called CAR T-cell therapy. CAR T-cell therapy is a type of immunotherapy. It uses infection-fighting cells from the body’s immune system to target cancer cells. The infection-fighting cells used in this study are called T cells. Scientists insert a protein called a chimeric antigen receptor (CAR) into T cells to give them the ability to kill cancer cells. The CAR T-cell target in this study is a particle called B7-H3. B7-H3 is found on many different types of pediatric solid tumors.

Purpose of this clinical trial

The main purpose of 3CAR is to find out if this type of immunotherapy is safe for pediatric patients with solid tumors. We also want to learn if it is effective in fighting solid tumors.

Eligibility overview

• 21 years old or younger*
• Relapsed or refractory B7-H3-positive solid tumor

*First 3 patients must be at least 12 years old.