NCT01109095: HERT-GBM

Administration of HER2 Chimeric Antigen Receptor Expressing CMV-Specific Cytotoxic T Cells Ins Patients With Glioblastoma Multiforme (HERT-GBM)

Completed Phase 1 Last updated 24 April 2019

What this trial tests

Phase 1 trial testing HER.CAR CMV-specific CTLs in Glioblastoma Multiforme (GBM) in 16 participants. Completed in 7 March 2018.

Timeline

1 October 2010

Primary endpoint
1 June 2014

7 March 2018

Quick facts

Lead sponsor	Baylor College of Medicine
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	16
Start date	1 October 2010
Primary completion	1 June 2014
Estimated completion	7 March 2018
Sites	2 locations across United States

Drugs / interventions tested

• HER.CAR CMV-specific CTLs — full drug profile →

Conditions studied

• Glioblastoma Multiforme (GBM) — all drugs for Glioblastoma Multiforme (GBM) →

Sponsor

Baylor College of Medicine

Who can join

Eligibility, any sex, with Glioblastoma Multiforme (GBM). Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Number of subjects with dose limiting toxicity after CTL infusion
  Time frame: 6 weeks
  To evaluate the safety of escalating doses of autologous CMV-specific cytotoxic T-lymphocytes (CTL) genetically modified to express chimeric antigen receptors (CAR) targeting the HER2 molecule in patients with HER2-positive Glioblastoma multiforme (GBM: WHO grade IV), who have recurrent or progressive disease after front line therapy.

Sponsor's own description

This study is for patients that have a type of brain cancer called glioblastoma multiforme (GBM).

The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. This research study combines two different ways of fighting cancer: antibodies and T cells. Antibodies are types of proteins that protect the body from infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including cells infected with viruses and tumor cells. Both antibodies and T cells have been used to treat patients with cancers. They have shown promise, but have not been strong enough to cure most patients.

The antibody used in this study is called anti-HER2 (Human Epidermal Growth Factor Receptor 2). This antibody sticks to GBM cells because of a substance on the outside of these cells called HER2. Up to 80% of GBMs are positive for HER2. HER2 antibodies have been used to treat people with HER2-positive cancers. For this study, the HER2 antibody has been changed so that instead of floating free in the blood it is now attached to T cells. When an antibody is joined to a T cell in this way it is called a chimeric receptor. These chimeric receptor-T cells seem to be able to kill tumors like GBM, but they don't last very long and so their chances of fighting the cancer are limited. Therefore, developing ways to prolong the life of these T cells should help them fight cancer.

We found that T cells work better if we also attach a protein called CD28 to the HER2 chimeric receptor (HER2-CAR). In this study we placed this HER2-CAR into T cells that were pre-selected for their ability to recognize Cytomegalovirus (CMV). This virus exists in most people. These CMV-specific cytotoxic T cells (CMV-T cells) will be more active since they will react to the virus as well as to tumor cells. These HER2-CD28 CMV-T cells are an investigational product not approved by the Food and Drug Administration.

The purpose of this study is to find the largest safe dose of HER2-CD28 CMV-T cells, to learn what the side effects are, and to see whether this therapy might help patients with GBM.

Publications & conference data

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

1. HER2-Specific Chimeric Antigen Receptor-Modified Virus-Specific T Cells for Progressive Glioblastoma: A Phase 1 Dose-Escalation Trial.
   Ahmed N, Brawley V, Hegde M, Bielamowicz K, et al · · 2017 · cited 712× · PMID 28426845 · DOI 10.1001/jamaoncol.2017.0184
2. Driving CAR T-cells forward.
   Jackson HJ, Rafiq S, Brentjens RJ. · · 2016 · cited 457× · PMID 27000958 · DOI 10.1038/nrclinonc.2016.36
3. CAR-cell therapy in the era of solid tumor treatment: current challenges and emerging therapeutic advances.
   Maalej KM, Merhi M, Inchakalody VP, Mestiri S, et al · · 2023 · cited 421× · PMID 36717905 · DOI 10.1186/s12943-023-01723-z
4. Rational development and characterization of humanized anti-EGFR variant III chimeric antigen receptor T cells for glioblastoma.
   Johnson LA, Scholler J, Ohkuri T, Kosaka A, et al · · 2015 · cited 356× · PMID 25696001 · DOI 10.1126/scitranslmed.aaa4963
5. Immunosenescence: a key player in cancer development.
   Lian J, Yue Y, Yu W, Zhang Y. · · 2020 · cited 354× · PMID 33168037 · DOI 10.1186/s13045-020-00986-z
6. Glioblastoma targeted therapy: updated approaches from recent biological insights.
   Touat M, Idbaih A, Sanson M, Ligon KL. · · 2017 · cited 308× · PMID 28863449 · DOI 10.1093/annonc/mdx106
7. Optimization of IL13Rα2-Targeted Chimeric Antigen Receptor T Cells for Improved Anti-tumor Efficacy against Glioblastoma.
   Brown CE, Aguilar B, Starr R, Yang X, et al · · 2018 · cited 260× · PMID 29103912 · DOI 10.1016/j.ymthe.2017.10.002
8. 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