Glioblastoma Clinical Trial
Official title:
Phase I Study of Monoclonal Antibondy (GS) 5745, an Matix Metalloproteinase 9 (MMP9) Mab Inhibitor, in Combination With Bevacizumab in Patients With Recurrent Glioblastoma
Despite surgery and first-line standard of care which consist of radiotherapy with
concomitant and adjuvant temozolomide, all patients with glioblastoma (GB) will experience
relapse. At the time of recurrence, therapeutic options include surgery or reirradiation in
selected cases, while in other cases, bevacizumab, approved by Food and Drug Administration
(FDA) but not European Medicines Agency (EMA), is the preferred option worldwide. Primary and
acquired resistance to bevacizumab has been explored without definitive finding.
Biomarkers able to predict response to antiangiogenic agents and particularly to bevacizumab
are an unmet medical need. We have showed that a low Matrix metallopeptidase 9 (MMP9) or a
high Matrix metallopeptidase 2 (MMP2) baseline plasma levels were associated with a high
response rate and a prolonged Progression-free survival (PFS) and overall survival (OS) in
recurrent GB patients treated with bevacizumab but not with cytotoxic chemotherapy. We also
observed that MMP9 plasma level decreased during bevacizumab treatment and tend to increase
at progression. Finally, in a retrospective analysis performed in the Avaglio trial (a
randomized phase III trial that tested bevacizumab versus placebo in addition to standard of
care in patients with newly diagnosed glioblastoma), a low plasma level of MMP9 at baseline
predicted consistently PFS and OS gain associated to bevacizumab.
These results are consistent with the role of MMP9 in vasculogenesis, since MMP9 contribute
to the recruitment of circulating endothelial and myeloid precursors, an alternative
vascularization process which is in part independent of the vascular endothelial growth
factor (VEGF) pathway.
Monoclonal Antibody (GS) 5745 is specifically directed against MMP9. First in human phase I
study has been completed. Development is ongoing.
Our results strongly support a role for MMP9 in the primary or acquired resistance to
bevacizumab. Therefore, we hypothesize that the Monoclonal Antibody GS5745 may overcome
resistance to bevacizumab through a specific inhibition of MMP9. While a preclinical program
is initiated in our lab, the proposed phase I study is the first step to analyze the
tolerance, determine the recommended dose of the combination and explore the impact of GS5745
on MMP9 plasma levels and multimodal imaging in patients with recurrent glioblastoma.
Objective:
Determine the safety profile and tolerability of GS5745 given in combination with a fixed
dose of bevacizumab in patients with recurrent GB in terms of Dose-Limiting Toxicities.
Multicenter, open label, dose-finding study of GS5745 in combination with bevacizumab
administered at a fixed dose; both drugs will be administered once every two weeks for a
total treatment duration of a maximum of 12 months.
Before initiation of each new dose level, a meeting between the sponsor, the coordinator, the
investigators and an independent external expert will take place to decide jointly the next
dose.
n/a
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT05664243 -
A Phase 1b / 2 Drug Resistant Immunotherapy With Activated, Gene Modified Allogeneic or Autologous γδ T Cells (DeltEx) in Combination With Maintenance Temozolomide in Subjects With Recurrent or Newly Diagnosed Glioblastoma
|
Phase 1/Phase 2 | |
| Completed |
NCT02768389 -
Feasibility Trial of the Modified Atkins Diet and Bevacizumab for Recurrent Glioblastoma
|
Early Phase 1 | |
| Recruiting |
NCT05635734 -
Azeliragon and Chemoradiotherapy in Newly Diagnosed Glioblastoma
|
Phase 1/Phase 2 | |
| Completed |
NCT03679754 -
Evaluation of Ad-RTS-hIL-12 + Veledimex in Subjects With Recurrent or Progressive Glioblastoma, a Substudy to ATI001-102
|
Phase 1 | |
| Completed |
NCT01250470 -
Vaccine Therapy and Sargramostim in Treating Patients With Malignant Glioma
|
Phase 1 | |
| Terminated |
NCT03927222 -
Immunotherapy Targeted Against Cytomegalovirus in Patients With Newly-Diagnosed WHO Grade IV Unmethylated Glioma
|
Phase 2 | |
| Recruiting |
NCT03897491 -
PD L 506 for Stereotactic Interstitial Photodynamic Therapy of Newly Diagnosed Supratentorial IDH Wild-type Glioblastoma
|
Phase 2 | |
| Active, not recruiting |
NCT03587038 -
OKN-007 in Combination With Adjuvant Temozolomide Chemoradiotherapy for Newly Diagnosed Glioblastoma
|
Phase 1 | |
| Completed |
NCT01922076 -
Adavosertib and Local Radiation Therapy in Treating Children With Newly Diagnosed Diffuse Intrinsic Pontine Gliomas
|
Phase 1 | |
| Recruiting |
NCT04391062 -
Dose Finding for Intraoperative Photodynamic Therapy of Glioblastoma
|
Phase 2 | |
| Active, not recruiting |
NCT03661723 -
Pembrolizumab and Reirradiation in Bevacizumab Naïve and Bevacizumab Resistant Recurrent Glioblastoma
|
Phase 2 | |
| Active, not recruiting |
NCT02655601 -
Trial of Newly Diagnosed High Grade Glioma Treated With Concurrent Radiation Therapy, Temozolomide and BMX-001
|
Phase 2 | |
| Completed |
NCT02206230 -
Trial of Hypofractionated Radiation Therapy for Glioblastoma
|
Phase 2 | |
| Completed |
NCT03493932 -
Cytokine Microdialysis for Real-Time Immune Monitoring in Glioblastoma Patients Undergoing Checkpoint Blockade
|
Phase 1 | |
| Terminated |
NCT02709889 -
Rovalpituzumab Tesirine in Delta-Like Protein 3-Expressing Advanced Solid Tumors
|
Phase 1/Phase 2 | |
| Recruiting |
NCT06058988 -
Trastuzumab Deruxtecan (T-DXd) for People With Brain Cancer
|
Phase 2 | |
| Completed |
NCT03018288 -
Radiation Therapy Plus Temozolomide and Pembrolizumab With and Without HSPPC-96 in Newly Diagnosed Glioblastoma (GBM)
|
Phase 2 | |
| Withdrawn |
NCT03980249 -
Anti-Cancer Effects of Carvedilol With Standard Treatment in Glioblastoma and Response of Peripheral Glioma Circulating Tumor Cells
|
Early Phase 1 | |
| Not yet recruiting |
NCT04552977 -
A Trail of Fluzoparil in Combination With Temozolomide in Patients With Recurrent Glioblastoma
|
Phase 2 | |
| Withdrawn |
NCT02876003 -
Efficacy and Safety of G-202 in PSMA-Positive Glioblastoma
|
Phase 2 |