Using CAR T cells to treat children with hard-to-treat solid tumors

Safety and Efficacy of B7H3 With IL-7 Receptor Alpha Signaling Chimeric Antigen Receptor T Cell (CMD03) in Relapse and Refractory Pediatric Solid Tumors

This study is testing a new type of immune cell treatment for children with hard-to-treat solid tumors to see if it can help them when other treatments haven't worked.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 9 (estimated)
• Ages: 1 Year to 25 Years
• Sex: All
• Sponsor: Chulalongkorn University (other)
• Drugs / interventions: CAR-T, chemotherapy, CAR T, chimeric antigen receptor, immunotherapy
• Locations: 1 site (Bangkok, Pathumwan)
• Trial ID: NCT06612645 on ClinicalTrials.gov

What this trial studies

This Phase 1 clinical trial evaluates the safety and early efficacy of CAR T cells engineered to target the B7-H3 antigen in children with solid tumors that have relapsed or are unresponsive to standard treatments. The study focuses on pediatric patients aged 1 to 25 years who have measurable B7-H3 positive solid tumors. Participants will receive B7H3-IL7Ra CAR-T cells after undergoing leukapheresis, and their response to the treatment will be monitored. This innovative approach aims to provide a new therapeutic option for a population with limited treatment alternatives.

Who should consider this trial

Good fit: Ideal candidates are children and young adults aged 1 to 25 years with B7-H3 positive solid tumors that have relapsed or are refractory after standard treatments.

Not a fit: Patients with solid tumors that do not express B7-H3 or those who have not undergone prior standard treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new hope for children with solid tumors that have not responded to existing therapies.

How similar studies have performed: While CAR T cell therapy has shown promise in other cancers, this specific approach targeting B7-H3 in pediatric solid tumors is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Participants must have B7-H3 positive solid tumor with measurable disease.

   \- B7-H3 expression will be evaluated by standard immunohistochemistry (IHC) or flow cytometry using a previously obtained sample.
2. Evidence of relapsed or refractory disease after standard first-line therapy
3. Age 1 - 25 years
4. Sex: Male or female
5. Performance status: Lansky or Karnofsky score not less than 50
6. Life expectancy not less than 12 weeks
7. Normal organ function

   * AST (SGOT) below 5 times the upper limit of normal (ULN)
   * ALT (SGPT) below 5 times the upper limit of normal (ULN)
   * Total bilirubin below 3 times the upper limit of normal (ULN)
   * Creatinine below 5 times the upper limit of normal (ULN)
   * SpO2 room air not less than 90%
8. Prior therapy wash-out before planned leukapheresis

   * Not less than 7 days post last chemotherapy/biologic therapy administration
   * 3 half-lives or 30 days, whichever is shorter after the last dose of antitumor antibody therapy
   * At least 30 days from most recent cellular infusion
   * All systemically administered corticosteroid treatment therapy must be stable or decreasing within 1 week prior to enrollment with a maximum of 0.5 mg/kg/day dose of methylprednisolone. Corticosteroid physiologic replacement therapy is allowed
9. Participants and/or legal guardians must have the ability to understand and willingness to sign a written informed consent and/or assent document

Exclusion Criteria:

1. Presence of greater than or equal to grade 3 cardiac dysfunction or symptomatic arrythmia requiring intervention
2. Presence of primary immunodeficiency or bone marrow failure syndrome
3. Presence of uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities, or psychiatric illness/social situations that would limit compliance with study requirements
4. Pregnant or breastfeeding women were excluded from this study because CAR-T cell therapy may be associated with the potential for teratogenic or abortifacient effects. Women of childbearing potential must have a negative serum pregnancy test. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CAR-T cells, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study. Participants of childbearing or child-fathering potential must be willing to practice birth control from the time of enrollment in this study and for four months after receiving CAR-T-cell infusion.
5. Serologic status reflecting active HIV, hepatitis B or C infection. Participants who are positive for hepatitis B core antibody, hepatitis B surface antigen or hepatitis C antibody must have negative PCR prior to enrollment.

Where this trial is running

Bangkok, Pathumwan

• King Chulalongkorn Memorial Hospital — Bangkok, Pathumwan, Thailand (RECRUITING)

Study contacts

• Principal investigator: Piti Techavichit, Associate Professor, MD — Chulalongkorn University
• Study coordinator: Piti Techavichit, Associate Professor, MD

Conditions: Pediatric Cancers, Solid Tumor Pediatric, CAR T cell, B7H3, IL-7 receptor alpha, Chimeric antigen receptor T cell, Adoptive cellular therapy, Solid tumor pediatric