NCT03283631: INTERCEPT

Intracerebral EGFR-vIII CAR-T Cells for Recurrent GBM

Terminated Phase 1 Last updated 5 April 2021

What this trial tests

Phase 1 trial testing EGFRvIII-CARs in Recurrent Glioblastoma in 2 participants. Terminated before completion.

Timeline

30 May 2018

Primary endpoint
19 September 2019

30 June 2020

Quick facts

Lead sponsor	Gary Archer Ph.D.
Phase	Phase 1
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	2
Start date	30 May 2018
Primary completion	19 September 2019
Estimated completion	30 June 2020
Sites	1 location across United States

Drugs / interventions tested

• EGFRvIII-CARs — full drug profile →

Conditions studied

• Recurrent Glioblastoma — all drugs for Recurrent Glioblastoma →
• Recurrent Gliosarcoma — all drugs for Recurrent Gliosarcoma →

Sponsor

Gary Archer Ph.D. — full company profile →

Who can join

18 and older, any sex, with Recurrent Glioblastoma or Recurrent Gliosarcoma. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

The goal of this protocol is to transfer autologous peripheral blood mononuclear cells (PBMCs) transduced with genes encoding a chimeric antigen receptor (CAR) that recognizes epidermal growth factor receptor variant III (EGFRvIII) tumor-specific antigen into patients with recurrent glioblastoma (GBM) following stereotactic radiosurgery (SRS). The CAR used is targeted to a tumor-specific mutation of the epidermal growth factor receptor, EGFRvIII, which is expressed on a subset of patients. Normal PBMCs derived from patients with GBM are genetically engineered with a viral vector encoding the CAR and infused directly into the patient's tumor with the aim of mediating regression of their tumors. Despite our CAR being targeted to a tumor specific antigen, given the prior toxicity using CARs that were not targeted to tumor-specific antigens, the investigators elected to begin with very low doses of cells. Enrollment on this study was suspended in April 2020 while an amendment to reduce the anticipated number of participants was under review and approved. The decision to terminate the study was made in January, 2021 to shift toward the next iteration of a related CAR T cell trial.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Glioblastoma in adults: a Society for Neuro-Oncology (SNO) and European Society of Neuro-Oncology (EANO) consensus review on current management and future directions.
   Wen PY, Weller M, Lee EQ, Alexander BM, et al · · 2020 · cited 908× · PMID 32328653 · DOI 10.1093/neuonc/noaa106
2. CAR T Cells for Solid Tumors: New Strategies for Finding, Infiltrating, and Surviving in the Tumor Microenvironment.
   Martinez M, Moon EK. · · 2019 · cited 653× · PMID 30804938 · DOI 10.3389/fimmu.2019.00128
3. Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives.
   Lin H, Liu C, Hu A, Zhang D, et al · · 2024 · cited 232× · PMID 38720342 · DOI 10.1186/s13045-024-01544-7
4. Harnessing the immune system in glioblastoma.
   Brown NF, Carter TJ, Ottaviani D, Mulholland P. · · 2018 · cited 178× · PMID 30393372 · DOI 10.1038/s41416-018-0258-8
5. Making CAR T Cells a Solid Option for Solid Tumors.
   Schmidts A, Maus MV. · · 2018 · cited 159× · PMID 30467505 · DOI 10.3389/fimmu.2018.02593
6. Harnessing the potential of CAR-T cell therapy: progress, challenges, and future directions in hematological and solid tumor treatments.
   Dagar G, Gupta A, Masoodi T, Nisar S, et al · · 2023 · cited 130× · PMID 37420216 · DOI 10.1186/s12967-023-04292-3
7. Adoptive Cell Therapy Targeting Neoantigens: A Frontier for Cancer Research.
   Wang Z, Cao YJ. · · 2020 · cited 127× · PMID 32194541 · DOI 10.3389/fimmu.2020.00176
8. CAR T Cell-Based Immunotherapy for the Treatment of Glioblastoma.
   Maggs L, Cattaneo G, Dal AE, Moghaddam AS, et al · · 2021 · cited 113× · PMID 34113233 · DOI 10.3389/fnins.2021.662064