GPC3-targeted CAR T cells armored with IL-15 and IL-21 for pediatric non‑CNS solid tumors
Immunotherapy for Solid Tumor Malignancies in Pediatrics Using Interleukin-15 and -21 Armored Glypican-3-specific Chimeric Antigen Receptor T Cells
This treatment will try personalized CAR T cells that target GPC3 and are engineered to make IL‑15 and IL‑21 in children and young adults with relapsed or refractory non‑CNS solid tumors that express GPC3.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 21 (estimated) |
| Ages | 1 Year to 26 Years |
| Sex | All |
| Sponsor | Seattle Children's Hospital Academic / other |
| Drugs / interventions | CAR T, chemotherapy, prednisone, chimeric antigen receptor, cyclophosphamide, fludarabine |
| Locations | 1 site (Seattle, Washington) |
| Trial ID | NCT07148050 on ClinicalTrials.gov |
What this trial studies
This Phase 1, open-label, non-randomized protocol enrolls pediatric and young adult patients with relapsed or refractory non‑CNS solid tumors that express glypican‑3 (GPC3). A blood sample is collected from each eligible patient and peripheral blood mononuclear cells are genetically modified to co‑express a GPC3‑specific CAR, interleukin‑15, interleukin‑21, and an inducible caspase‑9 safety switch (SC‑CAR.GPC3xIL15.21). The manufactured CAR T cells are infused and patients are monitored closely for safety, feasibility of manufacturing/delivery, and early signs of anti‑tumor activity. Preclinical comparisons showed that CAR T cells with IL‑15 and IL‑21 had improved tumor killing versus CAR T cells without those cytokines, and the product is investigational and not FDA approved.
Who should consider this trial
Good fit: Children and young adults with relapsed or refractory non‑CNS solid tumors that test positive for GPC3, with Lansky/Karnofsky ≥60% and life expectancy >16 weeks, are the intended participants.
Not a fit: Patients whose tumors do not express GPC3, those with active serious infections, prior organ transplantation, known HIV, or significant hypersensitivity to murine proteins are unlikely to be eligible or to benefit from this approach.
Why it matters
Potential benefit: If successful, these armored CAR T cells could persist longer and be more potent against GPC3‑positive tumors, potentially shrinking or controlling disease in some patients.
How similar studies have performed: CAR T therapies have been highly successful in blood cancers but have shown limited success in solid tumors; GPC3‑targeted CARs and cytokine 'armoring' have encouraging preclinical results and limited early clinical signals but remain largely experimental.
Eligibility criteria
Show full inclusion / exclusion criteria
1. Procurement Eligibility
Inclusion Criteria:
* Diagnosis of a solid tumor expressing GPC3
* Lansky or Karnofsky score of \>=60%
* Life expectancy of \>16 weeks
* Informed consent explained to, understood by and signed by patient/guardian.
For patients with hepatocellular carcinoma only:
* Barcelona Liver Cancer Stage A, B or C
* Child-Pugh Turcotte Score \<7
Exclusion Criteria:
* History of hypersensitivity reactions to murine protein-containing products OR presence of human anti-mouse antibody (HAMA) prior to enrollment for patients who have received prior therapy with murine antibodies.
* History of organ transplantation
* Known HIV positivity
* Active bacterial, fungal, or viral infection (except Hepatitis B or Hepatitis C virus infections)
2. Treatment eligibility
Inclusion Criteria:
* Lansky or Karnofsky score of \>=60%
* Life expectancy of \>16 weeks
* Informed consent explained to, understood by and signed by patient/guardian.
* Adequate organ function
* Adequate laboratory values
* Refractory or relapsed disease after treatment with up- front therapy and at least one salvage treatment cycle
* Recovered from acute toxic effects of all prior chemotherapy and investigational agents before entering this study
* Sexually active patients must be willing to utilize one of the more effective birth control methods for 12 months after the T-cell infusion.
* Informed consent explained to, understood by and signed by patient/guardian.
For patients with hepatocellular carcinoma only:
* Barcelona Liver Cancer Stage A, B or C
* Child-Pugh Turcotte Score \<7
Exclusion Criteria:
* History of hypersensitivity reactions to murine protein-containing products OR presence of human anti-mouse antibody (HAMA) prior to enrollment for patients who have received prior therapy with murine antibodies.
* History of organ transplantation
* Known HIV positivity
* Active autoimmune or inflammatory disorder
* Live vaccines within 30 days prior to enrollment
• Active bacterial, fungal, or viral infection (except Hepatitis B or Hepatitis C virus infections)
* Pregnancy or lactation
* Uncontrolled infection
* Systemic steroid treatment (≥ 0.5 mg prednisone equivalent/kg/day, dose adjustment or discontinuation of medication must occur at least 24hrs prior to CAR T cell infusion)
* Congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), unstable angina, serious uncontrolled cardiac arrhythmia, a myocardial infarction within 6 months prior to study entry or a history of myocarditis.
Where this trial is running
Seattle, Washington
- Seattle Children's Hospital — Seattle, Washington, United States (Recruiting)
Study contacts
- Study coordinator: Michelle Choe, MD
- Email: immunotherapy@seattlechildrens.org
- Phone: 206-987-2106
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.