"The confirmation of the initial safety profile of NOX-A12 in combination with radiotherapy in all patients of the first cohort is very encouraging."
Patient recruitment has been initiated for the second cohort of a phase I/II clinical trial (NCT04121455) of olaptesed pegol (NOX-A12) in addition to radiotherapy as treatment of patients with newly diagnosed brain cancer following confirmation from an Independent Data Safety Monitoring Board (DSMC) that the agent is safe, announced NOXXON Pharmaceuticals.
The safety analysis was completed after all patients in the first cohort received at least 4 weeks of treatment. The company is evaluating 3 different weekly doses of NOX-A12 in combination with external-beam radiotherapy across 3 cohorts in the clinical trial. The trial is being conducted in Germany.
"The confirmation of the initial safety profile of NOX-A12 in combination with radiotherapy in all patients of the first cohort is very encouraging," Aram Mangasarian, chief executive officer of NOXXON, said in a statement. "Following this analysis, the trial can progress to the second cohort as planned at the next dose level.”
The company plans to complete enrollment for the second cohort, which has already begun at participating trial sites, by the end of the first quarter of 2021 and the third cohort by mid-2021. They expect to obtain data on the first cohort of patients in October 2020.
In the first cohort of the trial, patients received a 200-mg weekly dose of NOX-A12 on a 4-week treatment schedule. The second cohort will receive a 400-mg weekly dose, and the third cohort will receive a 600-mg weekly dose.
The DSMC will evaluate the first patient enrolled to the second cohort after completing the 4-week treatment of NOX-A12 to determine if it is safe to recruit the remaining 2 patients for the cohort. Study completion is expected in September 2022.
The dose-escalation study aims to explore the safety and efficacy of NOX-A12 in combination with radiotherapy in patients with newly diagnosed grade IV glioblastoma of unmethylated MGMT promoter status who are either not amenable to resection or who received an incomplete tumor resection. The primary end point of the study is safety, and secondary end points include progression-free survival (PFS) at 6 months, median PFS, overall survival, plasma level of NOX-A12, quality of life, and neurologic functions.
To be eligible for the trial, patients must have a maximum ECOG performance status of 2 and a life expectancy of at least 3 months. They should also have a stable or decreasing dose of corticosteroids during the week prior to inclusion. Patients are not eligible if they have a contra-indication or known hypersensitivity to MRI contrast agents, NOX-A12, or polyethylene glycol. They are also not eligible if they’ve received cytostatic therapy (chemotherapy) within the past 5 years or have a history of other cancers, with the exception of adequately treated basal or squamous cell skin cancer, in situ cervical cancer, or another cancer but have been disease-free for ≥5 years.
Topline data have also been reported for NOX-A12 in combination with the immune checkpoint inhibitor pembrolizumab (Keytruda) as treatment of patients with metastatic colorectal cancer or pancreatic cancer. An additional study of NOX-A12 was initiated in September 2019 in combination with radiotherapy as treatment of patients with brain cancer.
NOX-A12 received an Orphan Drug designation in combination with radiotherapy for the treatment of certain brain cancers in both the United States and the European Union.
NOXXON Announces That Data Safety Monitoring Board Validates NOX-A12 Dose Escalation in Phase 1/2 Brain Cancer Study [news release]. Berlin, Germany: NOXXON Pharma; April 24, 2020. https://bwnews.pr/3cWjBuZ. Accessed April 27, 2020.