Olaptesed Pegol Continues to Improve Survival in Glioblastoma

Tumor in brain : © peterschreiber.media - stock.adobe.com

Olaptesed pegol (NOX-A12), a CXCL12 inhibitor, plus bevacizumab (Avastin), a VEGF inhibitor, and radiotherapy continue to demonstrate promising survival results in the treatment of patients with glioblastoma (GBM), according to 19-month follow-up of the phase 1/2 GLORIA study (NCT04121455).¹

The median overall survival (OS) has passed 19 months, and the 19-month survival rate in the olaptesed pegol, bevacizumab, and radiotherapy cohort is 10 times greater than a matched reference cohort receiving the standard of care (50% vs 5%, respectively).

“The survival data in the cohort receiving the combination of [olaptesed pegol], bevacizumab and radiotherapy has continued to improve with treatment or follow-up of enrolled brain cancer patients. Passing 19 months suggests a large survival benefit for patients on [olaptesed pegol]-based therapy since we are seeing more than an 80% increase in survival over the 10.5 months in the matched standard of care reference cohort of patients with the same profile as those we recruited into the study of [olaptesed pegol]: newly-diagnosed aggressive brain cancer with chemotherapy refractory tumors not amenable to complete surgical resection," said Aram Mangasarian, chief executive officer of TME Pharma, sponsor of the GLORIA study, in a press release.

The median OS for patients with newly diagnosed, chemotherapy-resistant, MGMT-unmethylated GBM ranged from 13.4-16.5 months with therapies in clinical development in the United States and European Union, according to TME Pharma.¹ Comparatively, Tumor Treating Fields, a therapy device for the treatment of GBM approved by the FDA in 2015, demonstrated a median OS of 20.9 months when combined with temozolomide in patients with newly diagnosed GBM regardless of methylation status, according to data from a study published in July 2023.²

About the GLORIA Study

GLORIA is a phase 1/2 dose-escalation study of olaptesed pegol plus radiation in patients with inoperable or partially resected first-line GBM who are unmethylated MGMT promoters. The study also has a 3-arm expansion group with patients with fully resected GBM and is evaluating the olaptesed pegol/radiation combination with bevacizumab or pembrolizumab (Keytruda).

Safety is the study’s primary end point. The secondary end points are progression-free survival (PFS) at 6 months, median PFS, changes in tumor vascularization, plasma concentration of olaptesed pegol, quality of life, and neurologic function.

Patients are eligible to participate if they have newly diagnosed, histologically confirmed, supratentorial WHO grade IV GBM and unmethylated promoter status. Patients must also have a maximum ECOG performance status of 2, have an estimated minimum life expectancy of 3 months, and use an effective form of birth control, if applicable. Patients are not eligible to participate if they have a contraindication to MRI contrast agents, a history of other cancers, clinically significant or uncontrolled cardiovascular disease, or uncontrolled concurrent illness.³

More updated data from the GLORIA study are expected to be announced in February 2024.¹

REFERENCES:

1. TME Pharma announces further improvement in median overall survival at 19 months follow-up in GLORIA brain cancer trial. News release. TME Pharma. December 20, 2023. Accessed December 20, 2023. http://tinyurl.com/yc27wz5m

2. Ballo, MT, Conlon, P, Lavy-Shahaf, G, et al. Association of Tumor Treating Fields (TTFields) therapy with survival in newly diagnosed glioblastoma: a systematic review and meta-analysis. J Neurooncol. 2023;164(1):1-9. doi:10.1007/s11060-023-04348-w

3. Glioblastoma treatment with irradiation and olaptesed pegol (NOX-A12 in MGMT unmethylated patients (GLORIA). ClinicalTrials.gov. Updated June 22, 2023. Accessed December 20, 2023. https://clinicaltrials.gov/study/NCT04121455