IL-15 and IL-21–armored GPC3-CAR T cell therapy for adults with GPC3-positive solid tumors

Immunotherapy For Adults With GPC3-Positive Solid Tumors Using Interleukin-15 And -21 Armored Glypican-3-Specific Chimeric Antigen Receptor Expressing Autologous T Cells

This trial tests whether CAR T cells engineered to target GPC3 and fortified with IL-15 and IL-21 can treat adults with GPC3-positive liver and other solid tumors.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 21 (estimated)
• Ages: N/A to 21 Years
• Sex: All
• Sponsor: Baylor College of Medicine (Academic / other)
• Drugs / interventions: CAR T, chemotherapy, prednisone, chimeric antigen receptor, radiation, cyclophosphamide, fludarabine, Cytoxan
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT06198296 on ClinicalTrials.gov

What this trial studies

Researchers collect a small amount of a participant's blood to grow T cells, then use a retrovirus to insert a GPC3-specific chimeric antigen receptor plus IL-15 and IL-21 genes into those cells. Patients receive short lymphodepleting chemotherapy with cyclophosphamide and fludarabine to make room for the infused cells, and the engineered CAR T cells are infused 48–72 hours after chemotherapy. This is a Phase 1 dose-escalation protocol designed to test safety and identify an appropriate dose, with laboratory testing of the manufactured cells before infusion. The trial is conducted at Baylor College of Medicine/Houston Methodist Hospital and enrolls adults with tumors that show GPC3 expression by immunohistochemistry.

Who should consider this trial

Good fit: Adults age 21 or older with GPC3-positive solid tumors confirmed by IHC, adequate performance status (Karnofsky/Lansky ≥60%), and life expectancy of at least 16 weeks are the intended candidates.

Not a fit: Patients whose tumors lack GPC3 expression, those with very poor functional status or who cannot tolerate lymphodepleting chemotherapy, and those with preexisting hypersensitivity to murine proteins are unlikely to benefit.

Why it matters

Potential benefit: If successful, the therapy could shrink GPC3-positive tumors and produce longer-lasting remissions than current options.

How similar studies have performed: Prior early-phase studies of GPC3-targeted CAR T cells have shown limited signals of activity in liver cancers, but adding IL-15 and IL-21 to CAR T cells is a relatively novel strategy with limited prior clinical data.

Eligibility criteria

Procurement Inclusion Criteria:

* Diagnosis of GPC3-positive\* solid tumors (as determined by immunohistochemistry with an extent score of \>=Grade 2 \[\>25% positive tumor cells\] and an intensity score of \>= 2 \[scale 0-4\]).
* Age ≥21 years
* Lansky or Karnofsky score ≥60%
* Life expectancy ≥16 weeks
* Barcelona Clinic Liver Cancer Stage A, B or C (- Child-Pugh-Turcotte score \<7 (for patients with hepatocellular carcinoma only)
* Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent \* GPC3 expression will be evaluated by standard immunohistochemistry (IHC) at Texas Patients's Hospital/Baylor College of Medicine, Department of Pathology for all patients to meet procurement eligibility. All patients will send at least 5 unstained slides.

Procurement Exclusion Criteria:

* History of hypersensitivity reactions to murine protein-containing products OR presence of human anti-mouse antibody (HAMA) prior to enrollment (only 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)

Treatment Inclusion Criteria:

* Diagnosis of GPC3-positive solid tumor
* Age ≥ 21 years
* Barcelona Clinic Liver Cancer Stage A, B or C
* Life expectancy of ≥ 12 weeks
* Lansky or Karnofsky score ≥ 60%
* Child-Pugh-Turcotte score \< 7
* Adequate organ function:
* Creatinine clearance as estimated by Cockcroft Gault or Schwartz ≥ 60 ml/min
* total bilirubin \< 3 times ULN for age
* INR ≤1.7 (for patients with hepatocellular carcinoma only)
* absolute neutrophil count \> 500/µl
* platelet count \> 25,000/µl (can be transfused)
* Hgb ≥ 7.0 g/dl (can be transfused)
* Pulse oximetry \>90% on room air
* 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, as determined by history and physical exam
* Sexually active patients must be willing to utilize one of the more effective birth control methods for 3 months after the T-cell infusion.
* Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent

Treatment Exclusion Criteria:

* Pregnancy or lactation
* Uncontrolled infection
* Systemic steroid treatment (greater than or equal to 0.5 mg prednisone equivalent/kg/day, dose adjustment or discontinuation of medication must occur at least 24hrs prior to CAR T cell infusion)
* Known HIV positivity
* Active bacterial, fungal or viral infection (except Hepatitis B or Hepatitis C virus infections)
* History of organ transplantation
* History of hypersensitivity reactions to murine protein-containing products OR presence of human anti-mouse antibody (HAMA) prior to enrollment (only patients who have received prior therapy with murine antibodies)

Where this trial is running

Houston, Texas

• Houston Methodist Hospital — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Premal Lulla, MD — Baylor College of Medicine
• Study coordinator: Premal Lulla, MD

Conditions Hepatoblastoma; Hepatocellular Carcinoma; Wilms Tumor; Malignant Rhabdoid Tumor; Yolk Sac Tumor; Rhabdomyosarcoma; Liposarcoma; Embryonal Sarcoma of Liver