Immunotherapy For Adults With GPC3-Positive Solid Tumors Using IL-15 and IL-21 Armored GPC3-CAR T Cells

Launched by BAYLOR COLLEGE OF MEDICINE · Dec 27, 2023

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment for adults with certain types of solid tumors that have a specific protein called GPC3 on their surface. The researchers are using a special kind of immune cell, called CAR T cells, which are modified to better recognize and attack cancer cells. They are combining these CAR T cells with two additional proteins, IL-15 and IL-21, to help the immune cells grow stronger and stay active in the body longer. The goal is to see if this new treatment can improve outcomes for patients with GPC3-positive tumors.

To be eligible for this trial, participants must be at least 21 years old and have a diagnosis of a solid tumor that shows GPC3 positivity. They should also have a good performance status, meaning they are able to carry out daily activities fairly well. Patients who have serious infections, are pregnant, or have had certain allergic reactions to previous treatments may not be able to join the study. Those who do participate will receive the modified CAR T cells and will be closely monitored for any side effects. Importantly, if any serious side effects occur, there is a safety measure in place to eliminate the CAR T cells quickly. This study is still in the early phases and has not yet begun recruiting participants.

Gender

ALL

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)