PHASE I STUDY OF EGFR806 CAR T CELL IMMUNOTHERAPY FOR RECURRENT/REFRACTORY SOLID TUMORS IN CHILDREN AND YOUNG ADULTS
STRIvE-01
What is the goal of the study?
This Phase I, open-label, non-randomized study will enroll pediatric and young adult patients with recurrent or refractory non-central nervous system (CNS) malignant solid tumors expressing epidermal growth factor (EGFR) to examine the safety and feasibility of administering autologous, peripheral blood-derived T cells that have been genetically modified using a self-inactivating (SIN) lentiviral vector to express a second generation (2G) EGFR806-specific chimeric antigen receptor (CAR) alone (Arm A) or in combination with a CD19-specific “driver” CAR (Arm B). The primary objectives of this study will be to assess the feasibility of deriving the cell products, the safety of the T-cell product infusion, and to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) of EGFR806 CAR T cells and EGFR806xCD19 CAR T cells and to describe the full toxicity profiles. The MTD will be determined using a 3+3 design for both Arms A and B; Arm B will proceed after establishment of the MTD for Arm A. Cohort advancement in Arms A and B will take place after all subjects in the current cohort have been followed for at least 28 days after infusion of genetically modified CAR T cells. Peripheral blood mononuclear cells (PBMC) will be isolated from an apheresis product obtained from the subject by apheresis after study enrollment. The T-cell products will be cryopreserved and release testing performed. T-cell dose cohort assignment will be made once the T-cell products meet release testing criteria and the subject meets criteria for T-cell infusions. The secondary objectives of this protocol are to study the in vivo engraftment and persistence of transferred cells by flow cytometry and quantitative polymerase chain reaction (PCR) for lentiviral vector-specific sequence. Additional secondary objectives include an assessment of anti-tumor activity using disease specific evaluations as well as the capacity of the co-expressed CD19 CAR to augment T-cell engraftment and prolong persistence as determined by the duration of B-cell aplasia. Should serious CAR T-cell mediated toxicities be encountered that are not controlled by medical management, the efficacy of cetuximab to eliminate CAR T cells through the EGFRt will be studied.
Who can participate in the study?
Please contact the study team listed below to learn more.