Anti-EGFRvIII synNotch Receptor Induced Anti-EphA2/IL-13Ralpha2 CAR (E-SYNC) T Cells

Description

PRIMARY OBJECTIVES:

I. To determine the safety of IV infused E-SYNC T cells for the treatment of EGFRvIII positive (EGFRvIII+) glioblastoma (GBM) (both cohorts).

SECONDARY OBJECTIVES:

I. To evaluate the feasibility of production and administration of E-SYNC T cells for the treatment of GBM (both cohorts).

II. To determine the local priming of E-SYNC T cells by prospective evaluation of GBM tissue and peripheral blood (cohort 2 only).

EXPLORATORY OBJECTIVES:

I. To determine antitumor responses and survival after infusion of E-SYNC T cells.

II. To evaluate development of immune responses against E-SYNC T cells favoring rejection.

III. To characterize the intratumoral immune landscape.

OUTLINE: This is a dose-escalation study utilizing E-SYNC T cells.

COHORT 1 (Dose Escalation): An estimated 6 to 15 participants with newly diagnosed EGFRvIII+ glioblastoma with O6-methylguanine-DNA methyl-transferase (MGMT) unmethylated status who have completed initial radiation therapy will be assigned to cohort 1. Participants undergo leukapheresis for the creation of E-SYNC T cells at least 2 weeks after completion of their non-investigational, standard of care radiation therapy.

COHORT 2 (Tissue Cohort): An estimated 5-8 participants with EGFRvIII+ glioblastoma recurrence after initial chemoradiation who need surgery will be assigned to cohort 2. Participants undergo leukapheresis for the creation of E-SYNC T cells more than 2 weeks after completion of their non-interventional, standard of care radiation therapy. Participants also undergo standard of care (SOC) surgical resection.

After completion of study treatment, participants are followed up on days 1, 3, 7, 10, 14, 21, and 28, then every 4 weeks in weeks 8-24, every 8 weeks in weeks 32-48, every 12 weeks in weeks 60-96, every 3 months in months 24-36, and then annually in years 3-15.

NOTE: The product formulation has been adjusted as of Protocol Version 2.1. Due to this formulation change, the first 3 participants enrolled at DL 1 prior to the adjustment will not be counted towards dose escalation analysis. These participants will continue for safety evaluation. Starting with the 4th participant, new enrollees will receive the updated formulation and continue to enroll at DL 1 to ensure consistency in dosing escalation decisions. The 4th participant will therefore serve as the 1st participant in updated DL1 cohort. Hence, enrollment will be paused after 4th participant is treated in updated DL1 formulation and monitoring and subsequent infusions will proceed per the staggered schedule