This is an open-label phase 1 study to assess the safety and feasibility of autologous T cells co-expressing two CARs targeting the cryptic EGFR epitope 806 and IL13Ra2 (referred to as "CART-EGFR-IL13Ra2 cells") in patients with EGFR-amplified glioblastoma, IDH-wildtype that has recurred following prior radiotherapy.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
67
autologous T cells transduced with a bicistronic lentiviral vector containing a murine scFv targeting EGFR and a humanized scFv targeting IL13Ra2
University of Pennsylvania
Philadelphia, Pennsylvania, United States
Number 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
Number of subjects with dose-limiting toxicities (DLTs)
Dose Escalation Phase only; Unacceptable toxicity as defined by the protocol
Time frame: 28 days following initial treatment with CART-EGFR-IL13Ra2 cells
Determination of maximum tolerated dose (MTD).
Dose Escalation Phase only: The maximum tolerated dose (MTD) is defined as the highest dose explored at which 0 or 1 DLT occurs in 6 evaluable subjects.
Time frame: 28 days following initial treatment with CART-EGFR-IL13Ra2 cellsnths
Determine the recommended dose for expansion (RDE).
Time frame: Up to 12 months following initial treatment with CART-EGFR-IL13Ra2 cells
Proportion of eligible subjects who receive all planned doses of CART-EGFR-IL13Ra2 cells.
Cohort 4 only
Time frame: 28 days following initial treatment with CART-EGFR-IL13Ra2 cells
Proportion of subjects who enroll on this study who received study treatment.
Evaluated based on the proportion of subjects who screen fail and those who receive any dose of CART-EGFR-IL13Ra2 cells.
Time frame: 12 months
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.
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Time frame: 3 months
Progression-Free Survival (PFS)
Per modified RANO criteria
Time frame: Up to 15 years following CART-EGFR-IL13Ra2 administration
Objective Response Rate (ORR)
Per modified RANO 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 modified RANO 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
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