Brain Cancer Hope: 19.9 Month Median Survival with New Combo

Human brain © Sergey Nivens - stock.adobe.com

Olaptesed pegol (NOX-A12), a CXCL12 inhibitor, plus the VEGF inhibitor bevacizumab (Avastin) and radiotherapy delivered an improved median overall survival (OS) of 19.9 months in patients with newly diagnosed glioblastoma (GBM), according to final OS data from the phase 1/2 GLORIA study (NCT04121455).¹

The survival rate in the olaptesed pegol cohort at 21 months is 10-fold greater than the matched reference cohort receiving standard-of-care (50% vs 5%). The matched reference cohort had a median OS of 10.5 months.

"With the survival data from the GLORIA cohort receiving [olaptesed pegol], bevacizumab, and radiotherapy reaching an unprecedented median overall survival of 19.9 months for the population of patients recruited, we see here compelling evidence of the potential of this combination to provide significant survival benefit to patients suffering from aggressive brain cancer over both standard of care and other competing therapies being developed clinically," said Aram Mangasarian, chief executive officer of TME Pharma, in a press release.

An FDA investigational new drug (IND) application and fast track designation request have been submitted. TME Pharma anticipates that they will receive approval for these by March 2024.

"The survival data formed a key part of our regulatory interactions, and following our recent constructive advice meeting with the FDA we are confident of being able to achieve our target of an approved IND and a decision on a fast track designation for [olaptesed pegol] by the end of Q1 2024. We believe the strong clinical data produced by the GLORIA trial along with a clear regulatory roadmap will allow us to attract the right partner and financing for [olaptesed pegol] to achieve its potential to become the best available therapy for glioblastoma patients,” Mangasarian added, in a press release.

About the GLORIA Trial

GLORIA is a phase 1/2 dose-escalation study of olaptesed pegol combined with radiation in patients with inoperable or partially resected newly diagnosed GBM with unmethylated MGMT status. The study also has a 3-arm expansion group for patients with fully resected GBM and is investigating the combination of olaptesed pegol and radiation with bevacizumab or pembrolizumab (Keytruda).²

The study’s primary end point is safety. Secondary end points include 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 enroll in the study if they have newly diagnosed, histologically confirmed, supratentorial WHO grade IV GBM with 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 ineligible for enrollment if they have a contraindication to MRI contrast agents, a history of other cancers, clinically significant or uncontrolled cardiovascular disease, or uncontrolled concurrent illness.

REFERENCES:

1. TME Pharma announces final median overall survival data reaching 19.9 months for NOX-A12 combination regimen in GLORIA brain cancer trial and survival rate 10-fold greater than standard of care. News release. TME Pharma N.V. February 2, 2024. Accessed February 6, 2024. http://tinyurl.com/59ta4vnu

2. Glioblastoma treatment with irradiation and olaptesed pegol (NOX-A12 in MGMT unmethylated patients (GLORIA). ClinicalTrials.gov. Updated June 22, 2023. Accessed February 6, 2024. https://clinicaltrials.gov/study/NCT04121455