LXF821 / University of Pennsylvania, Novartis - LARVOL DELTA

Repeated peripheral infusions of anti-EGFRvIII CAR T cells in combination with pembrolizumab remodels the tumor microenvironment in de novo glioblastoma (SNO 2023) - P1 | "Here, we conducted a phase I trial to study the safety and tolerability of CART-EGFRvIII cells administered concomitantly with the PD-1 inhibitor pembrolizumab in patients with newly diagnosed, EGFRvIII+ GBM (n=7). Together, these findings suggest that the combination of CAR T cells and PD-1 inhibition in GBM is safe and biologically active but, given the lack of efficacy, also indicate a need to consider alternative immunotherapeutic strategies. ClinicalTrials.gov registration: NCT03726515."

Biomarker • CAR T-Cell Therapy • Combination therapy • Tumor microenvironment • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • EGFR • PD-L1

Repeated peripheral infusions of anti-EGFRvIII CAR T cells in combination with pembrolizumab remodels the tumor microenvironment in de novo glioblastoma (SNO 2023) - P1 | "Here, we conducted a phase I trial to study the safety and tolerability of CART-EGFRvIII cells administered concomitantly with the PD-1 inhibitor pembrolizumab in patients with newly diagnosed, EGFRvIII+ GBM (n=7). Together, these findings suggest that the combination of CAR T cells and PD-1 inhibition in GBM is safe and biologically active but, given the lack of efficacy, also indicate a need to consider alternative immunotherapeutic strategies. ClinicalTrials.gov registration: NCT03726515."

Biomarker • CAR T-Cell Therapy • Combination therapy • Tumor microenvironment • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • EGFR • PD-L1

A phase I study of EGFRVIII-directed CAR T cells combined with PD-1 inhibition in patients with newly, diagnosed, MGMT-unmethylated glioblastoma: trial in progress (SNO 2019) - P1; "Peripheral IV infusions of 2x108 CART-EGFRvIII cells and 200mg pembrolizumab begin 2-3 weeks after completing radiation therapy. Secondary endpoints include overall survival, progression-free survival, and objective response rate. PROGRESS: At 5 June 2019, 2 patients have been enrolled and treated on study."

CAR T-Cell Therapy • Clinical • IO biomarker • P1 data • PD(L)-1 Biomarker • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • EGFR • PD-L1

Small-molecule toosendanin reverses macrophage-mediated immunosuppression to overcome glioblastoma resistance to immunotherapy. (PubMed, Sci Transl Med) - "Furthermore, TSN treatment sensitized GBM to Egfrviii chimeric antigen receptor (CAR) T cell therapy. These findings suggest that TSN may serve as a therapeutic compound that blocks tumor immunosuppression and circumvents tumor resistance to T cell-based immunotherapy in GBM and other solid tumors that warrants further investigation."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Immune Modulation • Oncology • Solid Tumor • LYN

CART-EGFRvIII + Pembrolizumab in GBM (clinicaltrials.gov) - P1; N=7; Completed; Sponsor: University of Pennsylvania; Active, not recruiting ➔ Completed; Trial completion date: Dec 2035 ➔ Feb 2021; Trial primary completion date: Aug 2035 ➔ Feb 2021

Clinical • Trial completion • Trial completion date • Trial primary completion date • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • MGMT • TERT

CART-EGFRvIII + Pembrolizumab in GBM (clinicaltrials.gov) - P1; N=7; Active, not recruiting; Sponsor: University of Pennsylvania; Trial completion date: Dec 2034 ➔ Dec 2035; Trial primary completion date: Dec 2020 ➔ Aug 2035

Clinical • Trial completion date • Trial primary completion date • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • EGFR • MGMT • TERT

CART-EGFRvIII + Pembrolizumab in GBM (clinicaltrials.gov) - P1; N=7; Recruiting; Sponsor: University of Pennsylvania; Active, not recruiting ➔ Recruiting

Clinical • Enrollment open • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • EGFR

CART-EGFRvIII + Pembrolizumab in GBM (clinicaltrials.gov) - P1; N=7; Not yet recruiting; Sponsor: University of Pennsylvania

New P1 trial • Biosimilar • Brain Cancer • Oncology • Solid Tumor

CART-EGFRvIII + Pembrolizumab in GBM (clinicaltrials.gov) - P1; N=7; Active, not recruiting; Sponsor: University of Pennsylvania; Recruiting ➔ Active, not recruiting

Enrollment closed • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

CART-EGFRvIII + Pembrolizumab in GBM (clinicaltrials.gov) - P1; N=7; Recruiting; Sponsor: University of Pennsylvania; Trial primary completion date: Dec 2019 ➔ Dec 2020

Clinical • Trial primary completion date

Autologous T Cells Redirected to EGFRVIII-With a Chimeric Antigen Receptor in Patients With EGFRVIII+ Glioblastoma (clinicaltrials.gov) - P1; N=11; Terminated; Sponsor: University of Pennsylvania; Phase classification: P=N/A ➔ P1

Clinical • Phase classification

Long-term Follow-up of Subjects Exposed to Lentiviral-based CART-EGFRvIII Gene-modified Cellular Therapy Products in Cancer Studies (clinicaltrials.gov) - P=N/A; N=3; Completed; Sponsor: University of Pennsylvania; Enrolling by invitation ➔ Completed; Trial completion date: Jan 2031 ➔ Jan 2018; Trial primary completion date: Jan 2031 ➔ Jan 2018

Clinical • Trial completion • Trial completion date • Trial primary completion date

Autologous T Cells Redirected to EGFRVIII-With a Chimeric Antigen Receptor in Patients With EGFRVIII+ Glioblastoma (clinicaltrials.gov) - P=N/A; N=11; Terminated; Sponsor: University of Pennsylvania; Trial completion date: Dec 2018 ➔ Apr 2018; Active, not recruiting ➔ Terminated; Trial primary completion date: Dec 2018 ➔ Apr 2018; Sponsor decision to terminate prior to completion to pursue combination therapies.

Clinical • Trial completion date • Trial primary completion date • Trial termination

CART-EGFRvIII + Pembrolizumab in GBM (clinicaltrials.gov) - P1; N=7; Recruiting; Sponsor: University of Pennsylvania; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open