This is an open-label phase 1 study to assess the safety, feasibility, pharmacokinetics and preliminary efficacy of autologous T cells co-expressing two CARs targeting the cryptic EGFR epitope 806 and IL3Ra2 (referred to as "CART-EGFR-IL13Ra2 cells"). Patients with newly diagnosed, EGFR-amplified, MGMT-unmethylated glioblastoma who have undergone maximal safe surgical resection will be approached for initial study participation. A two-step screening/eligibility process will be utilized. Following informed consent, subjects who meet Step #1 Eligibility Criteria will remain on study and complete a course of radiotherapy (60 Gy) without temozolomide as per their routine cancer care. If there is no overt evidence of disease recurrence/progression following radiotherapy, additional screening tests/procedures will be performed. Subjects who then meet Step #2 Eligibility Criteria will undergo apheresis collection to initiate cell product manufacturing and surgical placement of a CSF-Ventricular Reservoir to allow for intracerebroventricular injection of the CART-EGFR-IL13Ra2 cells. All subjects will receive a single fixed dose of CART-EGFR-IL13Ra2 cells on Day 0 via intracerebroventricular delivery.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
9
autologous T cells transduced with a bicistronic lentiviral vector containing a murine scFv targeting EGFR epitope 806 and a humanized scFv targeting IL13Ra2; both scFvs are fused to the 4-1BB and CD3ζ signaling domains.
University of Pennsylvania
Philadelphia, Pennsylvania, United States
RECRUITINGNumber of Subjects with treatment related adverse events using NCI Common Terminology Criteria for Adverse Events (CTCAE) V5.0
Type, frequency, severity, and attribution of adverse events
Time frame: Up to 15 years following CART-EGFR-IL13Ra2 administration
Occurrence of treatment-limiting toxicities (TLTs)
Time frame: 28 days post-CAR T cell administration
Proportion of enrolled subjects who receive study treatment as planned
Evaluated based on the proportion of subjects who screen fail and those who receive any dose of CART-EGFR-IL13Ra2 cells.
Time frame: 28 days following initial treatment with CART-EGFR-IL13Ra2 cells
Proportion of eligible subjects who receive study treatment as planned
Time frame: 28 days following initial treatment with CART-EGFR-IL13Ra2 cells
Frequency of manufacturing failures
Proportion of subjects with CART-EGFR-IL13Ra2 products that fail to meet the product release criteria, out of the number of subjects in whom manufacturing was attempted. Proportion of subjects with CART-EGFR-IL13Ra2 products that fail to meet the assigned dose, out of the number of subjects in whom manufacturing was attempted.
Time frame: 3 months
Progression-free Survival (PFS)
Per RANO 2.0 criteria
Time frame: Up to 15 years following CART-EGFR-IL13Ra2 administration
Overall Survival (OS)
Time from initial study treatment to the date of death from any cause.
Time frame: Up to 15 years following initial CART-EGFR-IL13Ra2 administration
Objective Response Rate (ORR)
Per RANO 2.0 criteria (in subjects with measurable disease at the time of study treatment); Proportion of subjects with confirmed CR and PR.
Time frame: Up to 12 months following CART-EGFR-IL13Ra2 administration
Duration of response (DOR)
Per RANO 2.0 criteria (in subjects with measurable disease at the time of study treatment); Time from the date when a response of confirmed CR/PR is first met to the date of confirmed disease progression, death or receipt of alternative treatment other than CART-EGFR-IL13Ra2 retreatment.
Time frame: Up to 15 years following initial CART-EGFR-IL13Ra2 administration
Abramson Cancer Center Clinical Trials Service
CONTACT
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