Olaptesed Pegol Delivers Promising Survival Data in GBM

Olaptesed pegol (NOX-A12), a CXCL12 inhibitor, in combination with the anti-VEGF agent bevacizumab (Avastin) and radiotherapy demonstrated a 13-fold improvement in overall survival (OS) compared with standard of care (SOC) in patients with glioblastoma.¹

Updated findings from the phase 1/2 GLORIA trial (NCT04121455) presented at the Society for Neuro-Oncology Annual Meeting 2023 showed that olaptesed pegol, bevacizumab, and radiotherapy delivered 67% OS at 18 months, while a SOC radiotherapy treatment achieved 5% survival and a median OS of 10.5 months. Furthermore, with a median follow-up of 18.3 months, 50% of patients remained alive.

Median progression-free survival (PFS) was 9 months vs 4 months in the experimental and SOC cohort, respectively. The radiographic overall response rate was 100%, and the mRANO3 response was 83.3%. There was 1 complete response per RANO, and 2 patients had tumor reduction over 99%. This led to 50% of patients in the expansion arm of the GLORIA trial having a complete or near-complete response.

"These unprecedented survival data demonstrate NOX-A12's clinical potential and are providing the basis for our forthcoming discussions with regulators on the next steps for NOX-A12's development in glioblastoma. We are looking forward to updating the market on our progress over the coming months, which we expect will include filings for an Investigational New Drug and expedited regulatory pathways,” said Aram Mangasarian, chief executive officer of TME Pharma, study sponsor and manufacturer of olaptesed pegol, in a press release.¹

About the Phase 1/2 GLORIA Trial

The phase 1/2 GLORIA trial is investigating the safety and efficacy of olaptesed pegol in combination with radiotherapy and bevacizumab in patients with newly diagnosed glioblastoma who have unmethylated MGMT status. The primary end point is safety and incidence of treatment-emergent adverse events as assessed by CTCAE. The secondary end points are PFS at 6 months, median PFS, median OS, tumor vascularization, plasma level of olaptesed pegol, quality-of-life, and neurologic function measured by the NANO scale.²

The study is broken down into 6 cohorts. Patients in cohorts 1-3 receive 200, 400, or 600 mg of olaptesed pegol intravenously for 26 weeks plus radiotherapy for weeks 1-6. Patients in the bevacizumab expansion cohort have not undergone resection or have undergone incomplete resection and receive 600 mg of olaptsed pegol weekly and 10 mg/kg of bevacizumab every 2 weeks for 26 weeks plus radiotherapy on weeks 1-6. Patients in the second expansion cohort have undergone complete resection and receive 600 mg of olaptesed pegol weekly for 26 weeks plus radiotherapy weeks 1-6. Patients in the third expansion cohort have undergone incomplete resection and receive 600 mg of olaptesed pegol weekly and 200 mg pembrolizumab every 3 weeks for 26 weeks plus radiotherapy for weeks 1-6.

Patients are eligible to participate if they have newly diagnosed, histologically confirmed, supratentorial WHO grade IV glioblastoma, are of unmethylated MGMT promoter status, have a maximum ECOG performance status of 2, and an estimated minimum life expectancy of 3 months. Patients are ineligible for the study if they have a history of other cancers, have received prior radiotherapy to the head, or have uncontrolled intercurrent illness.

REFERENCES:

1. TME Pharma announces additional data from NOX-A12 combination regimen in brain cancer presented at SNO 2023 annual meeting. News release. TME Pharma. November 18, 2023. Accessed November 21, 2023. https://tinyurl.com/aan35bx4

2. Glioblastoma treatment with irradiation and olaptesed pegol (NOX-A12) in MGMT unmethylated patients (GLORIA). ClinicalTrials.gov. Updated June 22, 2023. Accessed November 21, 2023. https://clinicaltrials.gov/study/NCT04121455